Atlas of Genetics and Cytogenetics in Oncology and Haematology


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CDC42 (cell division cycle 42 (GTP binding protein, 25kDa))

Identity

Other namesCDC42Hs
G25K
HGNC (Hugo) CDC42
LocusID (NCBI) 998
Location 1p36.12
Location_base_pair Starts at 22379120 and ends at 22419436 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description This gene can be found on Chromosome 1 at location 22,235,157-22,292,024.
Transcription The DNA sequence contains 6 exons and the transcript length is 1,512 bps translated to a 191 residues protein. Alternative splicing of this gene results in three transcript variants that encode two isoforms. The transcript variants 1 and 3 encode the same isoform 1. The variant 3 has an additional exon in the 5' UTR compared to variant 1. The variant 2 encodes isoform 2 and differs from variant 1 at the 3' region including a small part of the coding region and the entire 3' UTR.

Protein

Description CDC42 encodes a 21.3 kDa, 191 amino acids small GTPase protein that belongs to the Rho family of Ras GTPases superfamily. There are two isoforms produced by alternative splicing from a single gene. The isoform 1, also known as placental isoform, Cdc42p, Cdc42Hs or Cdc42a (Shinjo et al., 1990) has the same amino acid length than isoform 2 but differs from the isoform 2 as follows: 163 R (isoform 2) --> K (isoform 1) and at the C terminus in ten amino acids: 182-191 TQPKRKCCIF (isoform 2) --> PKKSRRCVLL (isoform 1). The isoform 2, also known as brain isoform, Cdc42b or G25K (Munemitsu et al., 1990), has been chosen as the 'canonical' sequence.
The contribution of CDC42 to cancer progression seems to be tissue specific due to it has been found to have pro-oncogenic and anti-oncogenic properties depending on cellular context.
CDC42 activity regulation:
CDC42 switches between an active GTP-bound state and inactive GDP-bound state. This cycle is regulated by its intrinsic GTPase activity and its interaction with three protein families: guanine exchange factors (GEFs), guanine dissociation inhibitors (GDIs) and GTPase activating proteins (GAPs) (Bishop and Hall, 2000). Due to the exchange of GDP to GTP by CDC42 itself occurs very slowly, GEFs promote such exchange from GDP- to GTP-bound state. GAPs increase the GTP hydrolysis activity. Furthermore, CDC42 is able to interact with membranes via post-translational C-terminal geranylgeranyl lipid modification, however it can be found as a soluble complex association with RhoGDI. Thus, RhoGDIs sequester CDC42-GDP in the cytoplasm through a transfer of geranylgeranyl moiety from membrane to GDI and inhibit its spontaneous GDP/GTP exchange activity. Additionally, CDC42 can be phosphorylated by diverse kinases which regulate its interaction with RhoGDIs (Forget et al., 2002; DerMardirossian and Bokoch, 2005). To date over 70 Rho-GEFs, 60 Rho-GAPs and 3 Rho-GDIs have been identified in mammals, reflecting the complexity of regulation of these classes of proteins.
Biochemical studies of CDC42 show that, in response to external signals originating from cell surface receptors and cell adhesion molecules, GEFs engage CDC42 and form macromolecular complexes with scaffolding proteins and/or kinases and with specific effector molecules triggering a signalling cascade to direct cellular responses (Cerione, 2004). CDC42 acts as a signal transduction convergence point in intracellular signalling networks, and mediates multiple signalling pathways, including tyrosine kinase receptors, heterodimeric G-protein coupled receptors (GPCR), cytokine receptors, integrins, and physical and chemical stress (Etienne-Manneville, 2004). The upstream signals include cytokines, growth factors, GPCR ligands, proteoglycans and integrins (Symons and Settleman, 2000).
CDC42 structure:
Rho proteins consist only of the GTPase domain and short N-terminal and C-terminal extensions. This family is defined by the presence of a Rho-type GTPases like domain located between the fifth β strand and the fourth α helix of their small GTPase domain (Valencia et al., 1991). A comparison of the RhoA-GDP and [Val14]RhoA-GTP[S] crystal structures, reveals that the conformational differences between the GTP and GDP-bound forms are restricted primarily to two surface loops, named switch regions I and II that correspond to CDC42 amino acids 26 and 59 (Bishop and Hall, 2000). Effector proteins utilize such differences to discriminate between the GTP- and GDP- bound forms, although they also interact with other regions of CDC42 protein. Nuclear magnetic resonance (NMR) structures of CDC42 bound to activated CDC42-associated tyrosine kinase (ACK) (amino acids 504-545) and WASP (amino acids 230-288) have provided a better understanding about Rho GTPase-effector interactions. ACK and WASP both contain the conserved GTPase-binding consensus site, the CRIB (CDC42/Rac-interactive binding) motif, which is present in many, though not all, Rac- and CDC42-binding proteins (Abdul-Manan et al., 1999; Mott et al., 1999). This motif is necessary, but not sufficient, for strong binding of the effector to CDC42.
CDC42 effectors:
To date, at least 23 proteins have been identified as potential effectors for CDC42 primarily using affinity chromatography and the yeast two-hybrid system. These proteins are: p70 S6 kinase; MLK2 and MLK3; MEKK1 and MEKK4; PAK1, PAK2, PAK3 and PAK4; MRCKα and MRCKβ; ACK1 and ACK2; PI3K; PLD; PLC-β2; WASP and N-WASP; MSE55 and BORGs; IQGAP1 and IQGAP2; and CIP-4 (Bishop and Hall, 2000).
The most common mechanism of effector activation by Rho GTPases appears to be the disruption of intramolecular autoinhibitory interactions, to expose functional domains within the effector protein.
CDC42 itself seems to be unable to discriminate downstream effectors because most of them, such as PAK, WASP, ACK and MLK3, have the same CDC42-interaction motif with similar binding affinity to active CDC42. So the specificity of CDC42 signalling seems to be dependent on: upstream signals that activate CDC42-GEFs; the interaction of these RhoGEFs with CDC42 effectors forming macromolecular complexes; the translocation of CDC42-effectors by RhoGEFs and RhoGDIs; and CDC42 signalling network components (Sinha and Yang, 2008).
Expression CDC42 isoform 1 is the most commonly studied form and it is expressed ubiquitously, whereas the isoform 2 is restricted to the brain (Wennerberg and Der, 2004).
Localisation In mammalian cells CDC42 is predominantly localized at Golgi apparatus but it has been also localized at the plasma membrane and on numerous vesicular structures dispersed throughout the cytosol (Erickson et al., 1996; Osmani et al., 2006).
Function CDC42 is one of the best characterized members of Rho family. Their involvements in regulating actin cytoskeleton and cell polarity are the best studied functions. In this context, CDC42 plays a role in a wide variety of cellular processes that are dependent on the actin cytoskeleton, such as cytokinesis, phagocytosis, cell migration, morphogenesis, chemotaxis and axon guidance.
Physiologically, CDC42 is implicated in other essential cellular processes such as axon myelination, intracellular trafficking, gene transcription, cell-cycle regulation and cell fate determination. However, the contribution of CDC42 in these different cellular processes could be cell-type specific (Wang and Zheng, 2007; Heasman and Ridley, 2008).
Deregulation of CDC42 is found in several pathogenic processes such as cancer, neurodegenerative disorders and cardiovascular disease (Boettner and Van Aelst, 2002; Broman et al., 2007).
Role in actin cytoskeleton organization: regulation of filopodium formation:
CDC42 regulates signal transduction pathways linking various membrane receptors to the finally filopodia formation in many cell types. Filopodia are thin protrusions that contain parallel bundles of actin filaments that extend from the leading edge in many migratory cells being able to function as sensory probes or in the establishment of cell-cell contacts, for example in axon guidance and neurite extension (Gupton and Gertler, 2007).
CDC42 induces actin polymerization to the filopodia formation by binding to Wiskott-Aldrich syndrome protein (WASP) or through the insulin-receptor substrate p53 (IRSp53) Tyr kinase to induce branched actin filaments using the actin-related protein-2/3 (ARP2/3) complex. CDC42 also induces actin polymerization by activation of mammalian diaphanous2 (mDia2). Moreover, CDC42-mediated activation of the Ser/Thr kinase PAK (p21-activated kinase) phosphorylates LIM kinase (LIMK), which phosphorylates and inhibits cofilin, thereby regulating actin filament turnover. In the neural growth cone, CDC42 might result in reduced cofilin phosphorylation by unknown mechanism, thereby stimulating actin polymerization and filopodium formation (Heasman and Ridley, 2008).
Role in axon myelination:
The formation of myelin sheaths in the central nervous system is the result of a complex series of events involving oligodendrocyte progenitor cell (OPC) proliferation, directed migration, and the morphological changes associated with axon ensheathment and myelination. Ablation of CDC42 in cells of the oligodendrocyte lineage leads to the formation of a unique and stage-specific myelination phenotype. This is characterized by the extraordinary enlargement of the inner tongue of the oligodendrocyte process and concomitant formation of a myelin outfolding as a result of abnormal accumulation of cytoplasm in this region (Thurnherr et al., 2006). Furthermore, OPCs, oligodendrocytes, and Schwann cells use actin polymerization-driven protrusion dependent on CDC42 effector N-WASP to advance in the processes for motility in the developing nervous system. In addition, it has been also demonstrated that p34 (a component of the Arp2/3 complex), WASP/WAVE proteins, actin, alpha-tubulin, Rac, CDC42, vinculin, and focal adhesion kinase are detected in water-shocked myelin purified from brain, so the same mechanism could be implicated in ensheathing axons at myelination (Bacon et al., 2007).
Role in migration and chemotaxis:
CDC42 has been involved in chemotaxis and directed migration of several cell types both in vitro and in vivo, including macrophages, T cells, fibroblasts and D melanogaster haemocytes (Heasman and Ridley, 2008). In macrophages, inhibition of CDC42 blocks chemotaxis toward CSF gradient without affecting mobility. Furthermore, CDC42 deletion in primary mouse embryonic fibroblasts (MEFs) causes abnormal cell spreading, reduced adhesion to fibronectin, defective mobility in wound healing, and decreases chemotaxis toward a serum gradient. These effects are associated with deficiencies of PAK1, GSK3β, myosin light chain and FAK phosporylation (Yang et al., 2006). In addition, an increase in CDC42 activity can stimulate migration speed, for example in neutrophils isolated from Cdc42GAP-knockout mice (Szczur et al., 2006). Conversely, directed migration of CDC42-null fibroblastoid cells has been reported to be normal (Wang and Zheng, 2007).
Role in cell polarity:
Polarity is involved in essentially every aspect of cell and developmental biology. All cell types polarize, at least transiently, during division or to generate specialized shapes and functions in proliferation, differentiation and morphogenesis. Moreover although the functional characteristics of cell polarity are extremely variable, depending on the cell type and the biological context, CDC42 has stood out as playing a central role in controlling of multiple signal transduction pathways which drives to cell polarity in all cell eukaryotic cells, irrespective of the biological context (Etienne-Manneville, 2004).
CDC42 seems to function primarily through the polarity protein partitioning-defective-6 (PAR6) and thereby with PAR3 and/or atypical protein kinase C (aPKC) isoforms to induce polarity in several cellular contexts (Goldstein and Macara, 2007). However, CDC42 can also function independently of the PAR complex through its effector myotonic-dystrophy-kinase-related CDC42-binding kinase (MRCK) (Gomes et al., 2005).
Role in cell cycle regulation and survival:
CDC42 is important in cell cycle through its involvement in G1/S-phase transition and its role in mitosis (Jaffe and Hall, 2005; Olson et al., 1995).
CDC42 blocks G1 progression in a variety of mammalian cell types, but the mechanisms are cell-type dependent and have proven difficult to elucidate. Multiple pathways seem to link CDC42 to the control of cyclin-D1 levels. The transcription of cyclin D1 is controlled by the ETS, AP-1 and nuclear factor-kappaB (NFkappaB), and many studies have been identified pathways that link CDC42 to these transcription factors (Perona et al., 1997; Sahai and Marshall, 2002). Furthermore, CDC42 stimulated the expression of cyclin E through its effector p70 S6 kinase (Chou et al., 2003).
During mitosis, spindle microtubules interact with chromosomes at the kinetochore, a complex of at least 50 proteins that includes the CDC42-specific effector mDia3. Inhibition of CDC42 or depletion of mDia3 causes a mitotic arrest in which many chromosomes are not properly attached to microtubules (Yasuda et al., 2004).
Furthermore, MEFS produced by gene targeting as CDC42 loss cell model are defective in G1/S-phase transition and survival, correlating with deficient NFkappaB transcription and defective JNK, p70 S6 kinase and ERK 1/2 activation (Yang et al., 2006). Moreover, in Cdc42GAP-/- hematopoietic stem/progenitor cells, the decrease in number of cells is associated with increased apoptosis of these cells and the activation of JNK-mediated apoptotic machinery (Wang et al., 2006).
Role in cell fate determination:
CDC42 is essential for skin progenitor cell differentiation into the hair follicle lineage by regulating beta-catenin turnover through CDC42-Par6-Par3-PKC ς-glycogen synthase kinase 3β signalling pathway (Wu et al., 2006). Moreover, CDC42 is important in the neural cell fate determination through the regulation of polarity following cell division at the apical surface mediated by the Par6-Par3-aPKC complex (Capello, 2006). Finally, conditional knock out of CDC42 in the bone marrow causes defects in multiple hematopoietic lineages, suppressing erythropoiesis but increasing myelopoiesis (Yang et al., 2007).
Role in intracellular trafficking:
In mammals, CDC42 is localized predominantly at Golgi complex. In Golgi apparatus, the activated form of CDC42 is able to associate with COPI complex. This complex is important in vesicle trafficking because regulates the intracellular trafficking and processing of EGF receptor. Several studies have demonstrated that CDC42 regulates polarized (basolateral) transport in Madin-Darby canine kidney (MDCK) cells. In addition, disruption of CDC42 function also inhibited both the basolateral transport of the low-density lipoprotein receptor and retrograde transport from the Golgi to the ER. Despite these clues, the underlying mechanistic role of CDC42 in trafficking remains unknown (Cerione, 2004).
Furthermore, secramine, a molecule that inhibits membrane traffic out of the Golgi apparatus, inhibits activation of CDC42, mimicking the effects of dominant-negative CDC42 expression on protein export from the Golgi and on Golgi polarization in migrating cells (Pelish et al., 2006).
Role in transcriptional control:
The activation of many Rho effector proteins results in the modulation of the activity of several transcription factors that play an important role at various levels of Rho signalling implicating them in many cellular functions (Benitah et al., 2004). Specifically, CDC42 is implicated in the regulation of several transcription factors such as NFkappaB, STAT3 and SRF. CDC42 is able to activate the NFkappaB pathway through JNK signalling dependent pathway by a mechanism that involves phosphorylation of IκBα and translocation of p50/p50 and p50/p65 dimers to the nucleus (Perona et al., 1997). In addition, the silencing of CDC42 in two bladder cancer cell lines decrease phosphorylation levels of the transcription factor STAT3 leading to the inhibition of the cellular proliferation and the induction of apoptosis (Wu et al., 2008). The constitutively active form of CDC42, Cdc42.V12, induces transcription via SRF through JNK/SAPK activation and acts synergistically at the c-fos serum response element (SRE) with signals that activate TCF (ternary complex factor) (Hill et al., 1995).
Recently, it has been described a novel mechanism of transcriptional regulation mediated by CDC42 through the promoter hypermethylation of the ID4 gene in a colorectal cancer cell line (Gomez del Pulgar et al., 2008).
Dual role in cancer:
It has been suggested that the contribution of CDC42 in tumour progression is tissue-specific. Depending on the cellular context, this Rho GTPase promotes or inhibits tumour progression. However, there are more cell types where CDC42 is a pro-oncogenic factor (Vega and Ridley, 2008).
CDC42 contributes to cancer development through its different roles in: intracellular trafficking, cell cycle regulation and survival, polarity, migration and transcriptional control (Vega and Ridley, 2008).
1. Intracellular trafficking: This process has been associated with the control of cell growth by the regulation of the processing and degradation of EGF receptor. The overexpression of a mutant form of CDC42 (F28L), which dissociates from GDP at a rate that is at least 50-fold faster than wild-type CDC42, produces an accumulation of EGF receptors. This accumulation causes an excessive mitogenic signalling through the Ras-Erk pathway that leads to cellular transformation (Wu et al., 2003). In this context, CDC42 stimulates and contributes to Ras-induced transformation in mouse fibroblasts in vitro (Qiu et al., 1997).
2. Cell cycle regulation and apoptosis: Many of the effects of Rho GTPases on G1 progression are thought to reflect the crucial role of anchorage- or adhesion-dependent signals for cell proliferation (Jaffe and Hall, 2005). Indeed, CDC42 could affect cell cycle progression by regulating chromosome misalignment during cell division, leading to multinucleated cells (Yasuda et al., 2006). Moreover, CDC42 contributes to immune escape of cancer as mediator of resistance to cytotoxic T lymphocytes (CTL)-mediated growth suppression of MEFs and HCT116 colorectal cancer cells. This event occurs through the prevention of CTL -induced apoptosis via mitogen-activated protein kinase (MAPK) signalling and posttranscriptional stabilization of Bcl-2 (Marques et al., 2008). By contrast, the overexpression of the active form of CDC42 in Jurkat T lymphocytes induces apoptosis through a JNK-dependent signaling pathway leading to caspase activation (Chuang et al., 1997).
3. Polarity and migration: CDC42 is predicted to inhibit invasion by promoting epithelial polarity, yet conversely also stimulated migration. Indeed, CDC42 contributes to cancer cell invasion in single cells with a mesenchymal morphology in vitro. It is also important for collective cancer cell invasion, where it acts through its effector MRCK to stimulate actomyosin contractility (Friedl and Wolf, 2003). In addition Rho activity alteration (RhoA, Rac1 and CDC42) has been linked with loss of polarity, an important fate in epithelial-mesenchymal transition (EMT) (Patel et al., 2005).
4. Transcriptional control: The implication of CDC42 in gene transcription has been also proposed as a mechanism of participation in tumour progression (Benitah et al., 2004). In this context, the activation of NFkappaB pathway by RhoA, Rac1 and CDC42 leads to the transcriptional expression of COX2, a protein highly implicated in cancer and inflammation processes (Benitah et al., 2003). Furthermore, RNAi-mediated inhibition of CDC42 produces a significant inhibition of cell proliferation and an induction of apoptosis in human in bladder cancer cell lines through the downregulation of STAT3 phosphorylated levels (Wu et al., 2008). Recently, the epigenetic transcriptional silencing of the putative tumour suppressor gene ID4 by CDC42 seems to be an important event in colorectal carcinogenesis (Gomez del Pulgar et al., 2008).
Finally, the involvement of CDC42 in the carcinogenic process is highly associated to aberrant expression and activity of the protein (Gomez del Pulgar et al., 2005; 2008).

Mutations

Note Unlike Ras proteins that are constitutively activated to oncoproteins by point mutations in human cancer, Rho family proteins are likely to be activated in vivo by different mechanisms such as overexpression of the GTPase or deregulation of the expression of regulatory proteins. Thus, no point mutations in the coding sequence of CDC42 gene were found in invasive breast and colon cancer samples (Rihet et al., 2001).

Implicated in

Entity Breast cancer
Oncogenesis CDC42 protein levels are highly increased in breast cancer compared with the corresponding normal tissue from the same patient (Fritz et al., 1999; 2002). This evidence is enforced with the results from a mouse model of breast carcinoma, where the expression of a dominant inhibitory mutant of CDC42 reduces the number of focal contacts, inhibits colony formation in soft agar in vitro and affects cell growth in vivo. Furthermore, this inactive form reduced intravasation into the peripheral blood and lung metastases (Bouzahzah et al., 2001).
ErbB1 and ErbB2 are often overexpressed in breast cancer and such overexpression is correlated with poor prognosis. Activated CDC42 contributes to the accumulation of ErbB1 in cells through the regulation of c-Cbl function. Thus, different therapeutic strategies targeting ErbB receptors and CDC42 have been proposed in this cancer type (Hirsch and Wu, 2007).
  
Entity Testicular cancer
Oncogenesis Western blot analyses revealed that CDC42 was significantly overexpressed in tumoral samples from 57 patients with testicular germ cell tumors compared with each non-tumor counterparts. The expression of CDC42 protein was significantly greater in tumors of higher stages than lower stages. Thus, CDC42 may be involved in the progression of testicular germ cell tumors (Kamai et al., 2004).
  
Entity Head and neck squamous cell carcinoma
Oncogenesis Immunohistochemical analysis has revealed that the protein CDC42 is overexpressed in head and neck cancer specimens (n=15). Moreover, CDC42 overexpression is found in premalignant and squamous cell cancer cell lines relative to normal keratinocytes (Abraham, 2001).
  
Entity Melanoma
Oncogenesis CDC42 protein expression is increased in tumoral samples from patients with fatal outcome using immunohistochemical assays. In this group a positive correlation is found between melanocytic CDC42 expression and Breslow thickness (Tucci et al., 2007). Besides, activation of CDC42 by surface antigens has been implicated in melanoma cell growth and invasion signals to promote cell-spreading. In keeping with this, autotoxin promotes invasiveness and angiogenesis through CDC42 in this cancer type (Eisenmann et al., 1999; Jung et al., 2002). In addition, DOCK10, a CDC42 GEF, activates CDC42 promoting amoeboid invasion of melanoma cells (Gadea et al., 2008).
  
Entity Colorectal cancer
Oncogenesis The protein levels of CDC42 are found to be overexpressed with high incidence (60%) in colorectal cancer samples. Such overexpression is significantly correlated with the histopathological grade of the tumor reflecting the plausible role of CDC42 in cell polarity and actin cytoskeleton. In addition, the CDC42 overexpression is associated with silencing of the putative tumor suppressor gene ID4 with statistical significance (Gomez del Pulgar et al., 2008). Moreover, leptin induces CDC42 activation promoting lamellopodium formation and concomitantly enhanced cell invasion in human colon cancer cells (Jaffe and Schwartz, 2008).
  
Entity Hepatocellular carcinoma
Oncogenesis Western blot expression of CDC42 in twenty patients with hepatocellular carcinoma (HCC) is higher in cancer tissues with HBV infection than para-cancerous liver tissues and cancer tissues without HBV infection (Chang et al., 2007). In addition, EB1 overexpression was associated with poorly differentiated HCC, which generally correlate with poor prognosis of these patients. Network analysis reveals that EB1 functions downstream of RhoA and CDC42 by interacting with mDia2 (Orimo et al., 2008). In the other hand, in a human HCC cell line, the protein BNIPL-2 is involved in the activation of CDC42 and enhances the migration and invasion of cancer cells in vitro, but also promotes cancer metastasis in vivo (Xie et al., 2007). By contrast, liver conditional CDC42 knock out mice suffer a chronic liver disease that leads to hepatocarcinogenesis. These tumors grow slowly and lack expression of nuclear beta-catenin. Lung metastases are observed at the late stage of carcinogenesis (Van Hengel et al., 2008).
  
Entity Lung cancer
Oncogenesis Although alterations of CDC42 expression or activation have not been described in any human lung tumor tissue yet, its inactivation or downregulation might be involved in lung tumor progression. Indeed, mRNA levels of CDC42 showed no change in adenomas, but were underexpressed in adenocarcinomas in mouse lung cancer considering as candidate "lung tumor progression" gene because its expression changes may specifically affect lung tumor progression in mice (Yao et al., 2002). In addition, in non small cell lung cancer (NSCLC) cell lines the tumor suppressor gene LKB1 maintains active CDC42 levels and downstream PAK phosphorylation to the regulation of epithelial cell polarity (Zang, 2008).
  
Entity Other cancer types
Oncogenesis Although to date there is no data available about the alteration of CDC42 expression or activation in patients with bladder cancer or lymphoma, there are some evidences that point CDC42 as an important factor in the development and progression of these cancer types. In the case of lymphomas, in anaplastic large cell lymphoma (ALCL) cell line, the oncogenic fusion protein NPM-ALK forms a complex with the GEF VAV1, enhancing its activation and consequently increasing CDC42 activation. This signalling regulates cell shape and migration. Genetic knockdown of CDC42 or pharmacological inhibition of CDC42 by secramine resulted in a cell cycle arrest and apoptosis of ALCL cells. Furthermore, CDC42 is necessary for the growth and the maintenance of already established lymphomas in vivo (Ambrogio et al., 2008).
In the case of bladder cancer, CDC42 silencing results in a significant inhibition of cell proliferation from G0/G1- to S-phase in two human bladder-cancer cell lines, EJ and T24, and an induction of apoptosis of EJ cells. These results suggest that CDC42 silencing may be a novel approach for therapy of bladder cancer (Wu et al., 2008).
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615

External links

Nomenclature
HGNC (Hugo)CDC42   1736
Cards
AtlasCDC42ID40012ch1p36
Entrez_Gene (NCBI)CDC42  998  cell division cycle 42
GeneCards (Weizmann)CDC42
Ensembl (Hinxton)ENSG00000070831 [Gene_View]  chr1:22379120-22419436 [Contig_View]  CDC42 [Vega]
ICGC DataPortalENSG00000070831
AceView (NCBI)CDC42
Genatlas (Paris)CDC42
WikiGenes998
SOURCE (Princeton)NM_001039802 NM_001791 NM_044472
Genomic and cartography
GoldenPath (UCSC)CDC42  -  1p36.12   chr1:22379120-22419436 +  1p36.1   [Description]    (hg19-Feb_2009)
EnsemblCDC42 - 1p36.1 [CytoView]
Mapping of homologs : NCBICDC42 [Mapview]
OMIM116952   
Gene and transcription
Genbank (Entrez)AF498962 AF498963 AK297465 AK303994 AK311375
RefSeq transcript (Entrez)NM_001039802 NM_001791 NM_044472
RefSeq genomic (Entrez)AC_000133 NC_000001 NC_018912 NT_032977 NW_001838573 NW_004929289
Consensus coding sequences : CCDS (NCBI)CDC42
Cluster EST : UnigeneHs.467637 [ NCBI ]
CGAP (NCI)Hs.467637
Alternative Splicing : Fast-db (Paris)GSHG0000227
Alternative Splicing GalleryENSG00000070831
Gene ExpressionCDC42 [ NCBI-GEO ]     CDC42 [ SEEK ]   CDC42 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP60953 (Uniprot)
NextProtP60953  [Medical]
With graphics : InterProP60953
Splice isoforms : SwissVarP60953 (Swissvar)
Domaine pattern : Prosite (Expaxy)RHO (PS51420)   
Domains : Interpro (EBI)P-loop_NTPase    Small_GTP-bd_dom    Small_GTPase    Small_GTPase_Rho   
Related proteins : CluSTrP60953
Domain families : Pfam (Sanger)Ras (PF00071)   
Domain families : Pfam (NCBI)pfam00071   
Domain families : Smart (EMBL)RHO (SM00174)  
DMDM Disease mutations998
Blocks (Seattle)P60953
PDB (SRS)1A4R    1AJE    1AM4    1AN0    1CEE    1CF4    1DOA    1E0A    1EES    1GRN    1GZS    1KI1    1KZ7    1KZG    1NF3    2ASE    2DFK    2KB0    2NGR    2ODB    2QRZ    2WM9    2WMN    2WMO    3GCG    3QBV    3VHL    4DID    4ITR    4JS0   
PDB (PDBSum)1A4R    1AJE    1AM4    1AN0    1CEE    1CF4    1DOA    1E0A    1EES    1GRN    1GZS    1KI1    1KZ7    1KZG    1NF3    2ASE    2DFK    2KB0    2NGR    2ODB    2QRZ    2WM9    2WMN    2WMO    3GCG    3QBV    3VHL    4DID    4ITR    4JS0   
PDB (IMB)1A4R    1AJE    1AM4    1AN0    1CEE    1CF4    1DOA    1E0A    1EES    1GRN    1GZS    1KI1    1KZ7    1KZG    1NF3    2ASE    2DFK    2KB0    2NGR    2ODB    2QRZ    2WM9    2WMN    2WMO    3GCG    3QBV    3VHL    4DID    4ITR    4JS0   
PDB (RSDB)1A4R    1AJE    1AM4    1AN0    1CEE    1CF4    1DOA    1E0A    1EES    1GRN    1GZS    1KI1    1KZ7    1KZG    1NF3    2ASE    2DFK    2KB0    2NGR    2ODB    2QRZ    2WM9    2WMN    2WMO    3GCG    3QBV    3VHL    4DID    4ITR    4JS0   
Human Protein AtlasENSG00000070831
Peptide AtlasP60953
HPRD00309
IPIIPI00007189   IPI00016786   IPI00910473   IPI00642590   
Protein Interaction databases
DIP (DOE-UCLA)P60953
IntAct (EBI)P60953
FunCoupENSG00000070831
BioGRIDCDC42
IntegromeDBCDC42
STRING (EMBL)CDC42
Ontologies - Pathways
QuickGOP60953
Ontology : AmiGOGolgi membrane  sprouting angiogenesis  cardiac conduction system development  keratinocyte development  GTPase activity  protein binding  GTP binding  cytoplasm  microtubule organizing center  cytosol  plasma membrane  plasma membrane  GTP catabolic process  Golgi organization  regulation of mitosis  nuclear migration  establishment or maintenance of cell polarity  epidermal growth factor receptor signaling pathway  small GTPase mediated signal transduction  axon guidance  blood coagulation  positive regulation of gene expression  negative regulation of gene expression  membrane  protein kinase binding  protein kinase binding  substantia nigra development  actin cytoskeleton organization  secretory granule  filopodium  macrophage differentiation  midbody  GTP-dependent protein binding  hair follicle morphogenesis  positive regulation of pseudopodium assembly  T cell costimulation  negative regulation of protein complex assembly  keratinization  mitogen-activated protein kinase kinase kinase binding  regulation of protein stability  thioesterase binding  positive regulation of cytokinesis  positive regulation of peptidyl-serine phosphorylation  apolipoprotein A-I receptor binding  adherens junction organization  cellular protein localization  establishment or maintenance of apical/basal cell polarity  multicellular organism growth  cytoplasmic ribonucleoprotein granule  Fc-gamma receptor signaling pathway involved in phagocytosis  negative regulation of epidermal growth factor receptor signaling pathway  regulation of protein catabolic process  muscle cell differentiation  identical protein binding  neuron projection  neuronal cell body  regulation of protein heterodimerization activity  positive regulation of neuron apoptotic process  positive regulation of phosphatidylinositol 3-kinase activity  innate immune response  apical part of cell  positive regulation of DNA replication  regulation of protein kinase activity  positive regulation of JNK cascade  filopodium assembly  positive regulation of metalloenzyme activity  neuron fate determination  actin filament bundle assembly  regulation of small GTPase mediated signal transduction  positive regulation of muscle cell differentiation  spindle midzone  regulation of filopodium assembly  establishment of Golgi localization  positive regulation of synapse structural plasticity  regulation of attachment of spindle microtubules to kinetochore  heart contraction  canonical Wnt signaling pathway  submandibular salivary gland formation  epithelial-mesenchymal cell signaling  hair follicle placode formation  extracellular vesicular exosome  positive regulation of hair follicle cell proliferation  organelle transport along microtubule  mitotic spindle  actin filament branching  epithelial cell-cell adhesion  positive regulation of intracellular protein transport  positive regulation of substrate adhesion-dependent cell spreading  
Ontology : EGO-EBIGolgi membrane  sprouting angiogenesis  cardiac conduction system development  keratinocyte development  GTPase activity  protein binding  GTP binding  cytoplasm  microtubule organizing center  cytosol  plasma membrane  plasma membrane  GTP catabolic process  Golgi organization  regulation of mitosis  nuclear migration  establishment or maintenance of cell polarity  epidermal growth factor receptor signaling pathway  small GTPase mediated signal transduction  axon guidance  blood coagulation  positive regulation of gene expression  negative regulation of gene expression  membrane  protein kinase binding  protein kinase binding  substantia nigra development  actin cytoskeleton organization  secretory granule  filopodium  macrophage differentiation  midbody  GTP-dependent protein binding  hair follicle morphogenesis  positive regulation of pseudopodium assembly  T cell costimulation  negative regulation of protein complex assembly  keratinization  mitogen-activated protein kinase kinase kinase binding  regulation of protein stability  thioesterase binding  positive regulation of cytokinesis  positive regulation of peptidyl-serine phosphorylation  apolipoprotein A-I receptor binding  adherens junction organization  cellular protein localization  establishment or maintenance of apical/basal cell polarity  multicellular organism growth  cytoplasmic ribonucleoprotein granule  Fc-gamma receptor signaling pathway involved in phagocytosis  negative regulation of epidermal growth factor receptor signaling pathway  regulation of protein catabolic process  muscle cell differentiation  identical protein binding  neuron projection  neuronal cell body  regulation of protein heterodimerization activity  positive regulation of neuron apoptotic process  positive regulation of phosphatidylinositol 3-kinase activity  innate immune response  apical part of cell  positive regulation of DNA replication  regulation of protein kinase activity  positive regulation of JNK cascade  filopodium assembly  positive regulation of metalloenzyme activity  neuron fate determination  actin filament bundle assembly  regulation of small GTPase mediated signal transduction  positive regulation of muscle cell differentiation  spindle midzone  regulation of filopodium assembly  establishment of Golgi localization  positive regulation of synapse structural plasticity  regulation of attachment of spindle microtubules to kinetochore  heart contraction  canonical Wnt signaling pathway  submandibular salivary gland formation  epithelial-mesenchymal cell signaling  hair follicle placode formation  extracellular vesicular exosome  positive regulation of hair follicle cell proliferation  organelle transport along microtubule  mitotic spindle  actin filament branching  epithelial cell-cell adhesion  positive regulation of intracellular protein transport  positive regulation of substrate adhesion-dependent cell spreading  
Pathways : BIOCARTAp38 MAPK Signaling Pathway [Genes]    Role of PI3K subunit p85 in regulation of Actin Organization and Cell Migration [Genes]    Role of MAL in Rho-Mediated Activation of SRF [Genes]    Ras Signaling Pathway [Genes]    How does salmonella hijack a cell [Genes]    Agrin in Postsynaptic Differentiation [Genes]   
Pathways : KEGGMAPK signaling pathway    Ras signaling pathway    Rap1 signaling pathway    Chemokine signaling pathway    Endocytosis    Axon guidance    VEGF signaling pathway    Focal adhesion    Adherens junction    Tight junction    T cell receptor signaling pathway    Fc gamma R-mediated phagocytosis    Leukocyte transendothelial migration    Neurotrophin signaling pathway    Regulation of actin cytoskeleton    GnRH signaling pathway    Non-alcoholic fatty liver disease (NAFLD)    Bacterial invasion of epithelial cells    Epithelial cell signaling in Helicobacter pylori infection    Pathogenic Escherichia coli infection    Shigellosis    Salmonella infection    Pathways in cancer    Viral carcinogenesis    Proteoglycans in cancer    Renal cell carcinoma    Pancreatic cancer   
REACTOMEP60953 [protein]
REACTOME PathwaysREACT_195021 Developmental Biology [pathway]
REACTOME PathwaysREACT_111045 Developmental Biology [pathway]
REACTOME PathwaysREACT_116125 Disease [pathway]
REACTOME PathwaysREACT_604 Hemostasis [pathway]
REACTOME PathwaysREACT_6900 Immune System [pathway]
REACTOME PathwaysREACT_111102 Signal Transduction [pathway]
Protein Interaction DatabaseCDC42
Wikipedia pathwaysCDC42
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)CDC42
SNP (GeneSNP Utah)CDC42
SNP : HGBaseCDC42
Genetic variants : HAPMAPCDC42
1000_GenomesCDC42 
ICGC programENSG00000070831 
CONAN: Copy Number AnalysisCDC42 
Somatic Mutations in Cancer : COSMICCDC42 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
DECIPHER (Syndromes)1:22379120-22419436
Mutations and Diseases : HGMDCDC42
OMIM116952   
MedgenCDC42
GENETestsCDC42
Disease Genetic AssociationCDC42
Huge Navigator CDC42 [HugePedia]  CDC42 [HugeCancerGEM]
Genomic VariantsCDC42  CDC42 [DGVbeta]
Exome VariantCDC42
dbVarCDC42
ClinVarCDC42
snp3D : Map Gene to Disease998
DGIdb (Curated mutations)CDC42
DGIdb (Drug Gene Interaction db)CDC42
General knowledge
Homologs : HomoloGeneCDC42
Homology/Alignments : Family Browser (UCSC)CDC42
Phylogenetic Trees/Animal Genes : TreeFamCDC42
Chemical/Protein Interactions : CTD998
Chemical/Pharm GKB GenePA26266
Clinical trialCDC42
Cancer Resource (Charite)ENSG00000070831
Other databases
Probes
Litterature
PubMed435 Pubmed reference(s) in Entrez
CoreMineCDC42
GoPubMedCDC42
iHOPCDC42

Bibliography

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Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42.
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An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1.
Olson MF, Ashworth A, Hall A.
Science. 1995 Sep 1;269(5228):1270-2.
PMID 7652575
 
Mammalian Cdc42 is a brefeldin A-sensitive component of the Golgi apparatus.
Erickson JW, Zhang C, Kahn RA, Evans T, Cerione RA.
J Biol Chem. 1996 Oct 25;271(43):26850-4.
PMID 8900167
 
The small GTPase Cdc42 initiates an apoptotic signaling pathway in Jurkat T lymphocytes.
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Mol Biol Cell. 1997 Sep;8(9):1687-98.
PMID 9307966
 
Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins.
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Genes Dev. 1997 Feb 15;11(4):463-75.
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Cdc42 regulates anchorage-independent growth and is necessary for Ras transformation.
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PMID 9154844
 
Structure of Cdc42 in complex with the GTPase-binding domain of the 'Wiskott-Aldrich syndrome' protein.
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Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas.
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Nat Cell Biol. 1999 Dec;1(8):507-13.
PMID 10587647
 
Rho GTPases are over-expressed in human tumors.
Fritz G, Just I, Kaina B.
Int J Cancer. 1999 May 31;81(5):682-7.
PMID 10328216
 
Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK.
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Nature. 1999 May 27;399(6734):384-8.
PMID 10360579
 
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PMID 10816416
 
Rho family GTPases: more than simple switches.
Symons M, Settleman J.
Trends Cell Biol. 2000 Oct;10(10):415-9. (REVIEW)
PMID 10998597
 
Motility-related proteins as markers for head and neck squamous cell cancer.
Abraham MT, Kuriakose MA, Sacks PG, Yee H, Chiriboga L, Bearer EL, Delacure MD.
Laryngoscope. 2001 Jul;111(7):1285-9.
PMID 11568556
 
Rho family GTPases regulate mammary epithelium cell growth and metastasis through distinguishable pathways.
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PMID 11844870
 
Mutation status of genes encoding RhoA, Rac1, and Cdc42 GTPases in a panel of invasive human colorectal and breast tumors.
Rihet S, Vielh P, Camonis J, Goud B, Chevillard S, de Gunzburg J.
J Cancer Res Clin Oncol. 2001 Dec;127(12):733-8.
PMID 11768613
 
The role of Rho GTPases in disease development.
Boettner B, Van Aelst L.
Gene. 2002 Mar 20;286(2):155-74. (REVIEW)
PMID 11943472
 
Phosphorylation states of Cdc42 and RhoA regulate their interactions with Rho GDP dissociation inhibitor and their extraction from biological membranes.
Forget MA, Desrosiers RR, Gingras D, Beliveau R.
Biochem J. 2002 Jan 15;361(Pt 2):243-54.
PMID 11772396
 
Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters.
Fritz G, Brachetti C, Bahlmann F, Schmidt M, Kaina B.
Br J Cancer. 2002 Sep 9;87(6):635-44.
PMID 12237774
 
Cdc42 and Rac1 are necessary for autotaxin-induced tumor cell motility in A2058 melanoma cells.
Jung ID, Lee J, Yun SY, Park CG, Choi WS, Lee HW, Choi OH, Han JW, Lee HY.
FEBS Lett. 2002 Dec 18;532(3):351-6.
PMID 12482591
 
RHO-GTPases and cancer.
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Nat Rev Cancer. 2002 Feb;2(2):133-42. (REVIEW)
PMID 12635176
 
Differentially expressed genes associated with mouse lung tumor progression.
Yao R, Wang Y, Lubet RA, You M.
Oncogene. 2002 Aug 22;21(37):5814-21.
PMID 12173053
 
ROCK and nuclear factor-kappaB-dependent activation of cyclooxygenase-2 by Rho GTPases: effects on tumor growth and therapeutic consequences.
Benitah SA, Valeron PF, Lacal JC.
Mol Biol Cell. 2003 Jul;14(7):3041-54.
PMID 12857884
 
Cdc42 promotes G1 progression through p70 S6 kinase-mediated induction of cyclin E expression.
Chou MM, Masuda-Robens JM, Gupta ML.
J Biol Chem. 2003 Sep 12;278(37):35241-7.
PMID 12842876
 
Tumour-cell invasion and migration: diversity and escape mechanisms.
Friedl P, Wolf K.
Nat Rev Cancer. 2003 May;3(5):362-74. (REVIEW)
PMID 12724734
 
Activated Cdc42 sequesters c-Cbl and prevents EGF receptor degradation.
Wu WJ, Tu S, Cerione RA.
Cell. 2003 Sep 19;114(6):715-25.
PMID 14505571
 
Rho GTPases in human cancer: an unresolved link to upstream and downstream transcriptional regulation.
Benitah SA, Valeron PF, van Aelst L, Marshall CJ, Lacal JC.
Biochim Biophys Acta. 2004 Dec 17;1705(2):121-32.
PMID 15588766
 
Cdc42: new roads to travel.
Cerione RA.
Trends Cell Biol. 2004 Mar;14(3):127-32. (REVIEW)
PMID 15003621
 
Cdc42--the centre of polarity.
Etienne-Manneville S.
J Cell Sci. 2004 Mar 15;117(Pt 8):1291-300. (REVIEW)
PMID 15020669
 
Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer.
Kamai T, Yamanishi T, Shirataki H, Takagi K, Asami H, Ito Y, Yoshida K.
Clin Cancer Res. 2004 Jul 15;10(14):4799-805.
PMID 15269155
 
Rho-family GTPases: it's not only Rac and Rho (and I like it).
Wennerberg K, Der CJ.
J Cell Sci. 2004 Mar 15;117(Pt 8):1301-12. (REVIEW)
PMID 15020670
 
Cdc42 and mDia3 regulate microtubule attachment to kinetochores.
Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, Ishizaki T, Narumiya S.
Nature. 2004 Apr 15;428(6984):767-71.
PMID 15085137
 
GDIs: central regulatory molecules in Rho GTPase activation.
DerMardirossian C, Bokoch GM.
Trends Cell Biol. 2005 Jul;15(7):356-63. (REVIEW)
PMID 15921909
 
Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells.
Gomes ER, Jani S, Gundersen GG.
Cell. 2005 May 6;121(3):451-63.
PMID 15882626
 
Rho GTPase expression in tumourigenesis: evidence for a significant link.
Gomez del Pulgar T, Benitah SA, Valeron PF, Espina C, Lacal JC.
Bioessays. 2005 Jun;27(6):602-13.
PMID 15892119
 
Rho GTPases: biochemistry and biology.
Jaffe AB, Hall A.
Annu Rev Cell Dev Biol. 2005;21:247-69. (REVIEW)
PMID 16212495
 
RhoGTPase activation is a key step in renal epithelial mesenchymal transdifferentiation.
Patel S, Takagi KI, Suzuki J, Imaizumi A, Kimura T, Mason RM, Kamimura T, Zhang Z.
J Am Soc Nephrol. 2005 Jul;16(7):1977-84.
PMID 15901767
 
The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface.
Cappello S, Attardo A, Wu X, Iwasato T, Itohara S, Wilsch-Brauninger M, Eilken HM, Rieger MA, Schroeder TT, Huttner WB, Brakebusch C, Gotz M.
Nat Neurosci. 2006 Sep;9(9):1099-107.
PMID 16892058
 
Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration.
Osmani N, Vitale N, Borg JP, Etienne-Manneville S.
Curr Biol. 2006 Dec 19;16(24):2395-405.
PMID 17081755
 
Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro.
Pelish HE, Peterson JR, Salvarezza SB, Rodriguez-Boulan E, Chen JL, Stamnes M, Macia E, Feng Y, Shair MD, Kirchhausen T.
Nat Chem Biol. 2006 Jan;2(1):39-46.
PMID 16408091
 
Rho GTPase CDC42 regulates directionality and random movement via distinct MAPK pathways in neutrophils.
Szczur K, Xu H, Atkinson S, Zheng Y, Filippi MD.
Blood. 2006 Dec 15;108(13):4205-13.
PMID 16931627
 
Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS.
Thurnherr T, Benninger Y, Wu X, Chrostek A, Krause SM, Nave KA, Franklin RJ, Brakebusch C, Suter U, Relvas JB.
J Neurosci. 2006 Oct 4;26(40):10110-9.
PMID 17021167
 
Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment.
Wang L, Yang L, Filippi MD, Williams DA, Zheng Y.
Blood. 2006 Jan 1;107(1):98-105.
PMID 16174757
 
Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin.
Wu X, Quondamatteo F, Lefever T, Czuchra A, Meyer H, Chrostek A, Paus R, Langbein L, Brakebusch C.
Genes Dev. 2006 Mar 1;20(5):571-85.
PMID 16510873
 
Gene targeting of Cdc42 and Cdc42GAP affirms the critical involvement of Cdc42 in filopodia induction, directed migration, and proliferation in primary mouse embryonic fibroblasts.
Yang L, Wang L, Zheng Y.
Mol Biol Cell. 2006 Nov;17(11):4675-85.
PMID 16914516
 
An essential role of Cdc42-like GTPases in mitosis of HeLa cells.
Yasuda S, Taniguchi H, Oceguera-Yanez F, Ando Y, Watanabe S, Monypenny J, Narumiya S.
FEBS Lett. 2006 Jun 12;580(14):3375-80.
PMID 16716304
 
N-WASP regulates extension of filopodia and processes by oligodendrocyte progenitors, oligodendrocytes, and Schwann cells-implications for axon ensheathment at myelination.
Bacon C, Lakics V, Machesky L, Rumsby M.
Glia. 2007 Jun;55(8):844-58.
PMID 17405146
 
Cdc42 regulates the restoration of endothelial adherens junctions and permeability.
Broman MT, Mehta D, Malik AB.
Trends Cardiovasc Med. 2007 Jul;17(5):151-6. (REVIEW)
PMID 17574122
 
Different expression of apoptotic proteins between HBV-infected and non-HBV-infected hepatocellular carcinoma.
Chang CS, Huang SM, Lin HH, Wu CC, Wang CJ.
Hepatogastroenterology. 2007 Oct-Nov;54(79):2061-8.
PMID 18251160
 
The PAR proteins: fundamental players in animal cell polarization.
Goldstein B, Macara IG.
Dev Cell. 2007 Nov;13(5):609-22. (REVIEW)
PMID 17981131
 
Filopodia: the fingers that do the walking.
Gupton SL, Gertler FB.
Sci STKE. 2007 Aug 21;2007(400):re5. (REVIEW)
PMID 17712139
 
Cdc42: an effector and regulator of ErbB1 as a strategic target in breast cancer therapy.
Hirsch DS, Wu WJ.
Expert Rev Anticancer Ther. 2007 Feb;7(2):147-57. (REVIEW)
PMID 17288526
 
Involvement of E-cadherin, beta-catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma.
Tucci MG, Lucarini G, Brancorsini D, Zizzi A, Pugnaloni A, Giacchetti A, Ricotti G, Biagini G.
Br J Dermatol. 2007 Dec;157(6):1212-6.
PMID 17970806
 
Cell type-specific functions of Rho GTPases revealed by gene targeting in mice.
Wang L, Zheng Y.
Trends Cell Biol. 2007 Feb;17(2):58-64. (REVIEW)
PMID 17161947
 
BNIPL-2 promotes the invasion and metastasis of human hepatocellular carcinoma cells.
Xie L, Qin W, Li J, He X, Zhang H, Yao G, Shu H, Yao M, Wan D, Gu J.
Oncol Rep. 2007 Mar;17(3):605-10.
PMID 17273740
 
Cdc42 critically regulates the balance between myelopoiesis and erythropoiesis.
Yang L, Wang L, Kalfa TA, Cancelas JA, Shang X, Pushkaran S, Mo J, Williams DA, Zheng Y.
Blood. 2007 Dec 1;110(12):3853-61.
PMID 17702896
 
The anaplastic lymphoma kinase controls cell shape and growth of anaplastic large cell lymphoma through Cdc42 activation.
Ambrogio C, Voena C, Manazza AD, Martinengo C, Costa C, Kirchhausen T, Hirsch E, Inghirami G, Chiarle R.
Cancer Res. 2008 Nov 1;68(21):8899-907.
PMID 18974134
 
DOCK10-mediated Cdc42 activation is necessary for amoeboid invasion of melanoma cells.
Gadea G, Sanz-Moreno V, Self A, Godi A, Marshall CJ.
Curr Biol. 2008 Oct 14;18(19):1456-65.
PMID 18835169
 
Cdc42 is highly expressed in colorectal adenocarcinoma and downregulates ID4 through an epigenetic mechanism.
Gomez Del Pulgar T, Valdes-Mora F, Bandres E, Perez-Palacios R, Espina C, Cejas P, Garcia-Cabezas MA, Nistal M, Casado E, Gonzalez-Baron M, Garcia-Foncillas J, Lacal JC.
Int J Oncol. 2008 Jul;33(1):185-93.
PMID 18575765
 
Mammalian Rho GTPases: new insights into their functions from in vivo studies.
Heasman SJ, Ridley AJ.
Nat Rev Mol Cell Biol. 2008 Sep;9(9):690-701. (REVIEW)
PMID 18719708
 
Leptin promotes motility and invasiveness in human colon cancer cells by activating multiple signal-transduction pathways.
Jaffe T, Schwartz B.
Int J Cancer. 2008 Dec 1;123(11):2543-56.
PMID 18767036
 
An immune escape screen reveals Cdc42 as regulator of cancer susceptibility to lymphocyte-mediated tumor suppression.
Marques CA, Hahnel PS, Wolfel C, Thaler S, Huber C, Theobald M, Schuler M.
Blood. 2008 Feb 1;111(3):1413-9.
PMID 17971488
 
Proteomic profiling reveals the prognostic value of adenomatous polyposis coli-end-binding protein 1 in hepatocellular carcinoma.
Orimo T, Ojima H, Hiraoka N, Saito S, Kosuge T, Kakisaka T, Yokoo H, Nakanishi K, Kamiyama T, Todo S, Hirohashi S, Kondo T.
Hepatology. 2008 Dec;48(6):1851-63.
PMID 18937283
 
Cellular signaling for activation of Rho GTPase Cdc42.
Sinha S, Yang W.
Cell Signal. 2008 Nov;20(11):1927-34. (REVIEW)
PMID 18558478
 
Continuous cell injury promotes hepatic tumorigenesis in cdc42-deficient mouse liver.
van Hengel J, D'Hooge P, Hooghe B, Wu X, Libbrecht L, De Vos R, Quondamatteo F, Klempt M, Brakebusch C, van Roy F.
Gastroenterology. 2008 Mar;134(3):781-92.
PMID 18325391
 
Rho GTPases in cancer cell biology.
Vega FM, Ridley AJ.
FEBS Lett. 2008 Jun 18;582(14):2093-101. (REVIEW)
PMID 18460342
 
RNA-interference-mediated Cdc42 silencing down-regulates phosphorylation of STAT3 and suppresses growth in human bladder-cancer cells.
Wu F, Chen Y, Li Y, Ju J, Wang Z, Yan D.
Biotechnol Appl Biochem. 2008 Feb;49(Pt 2):121-8.
PMID 17705801
 
The tumor suppressor LKB1 regulates lung cancer cell polarity by mediating cdc42 recruitment and activity.
Zhang S, Schafer-Hales K, Khuri FR, Zhou W, Vertino PM, Marcus AI.
Cancer Res. 2008 Feb 1;68(3):740-8.
PMID 18245474
 
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Contributor(s)

Written12-2008Fátima Valdés-Mora, Teresa Gómez del Pulgar, Juan Carlos Lacal
Translational Oncology Unit CSIC-UAM- La Paz Centro Nacional de Biotecnologia C/ Darwin 3, Campus de Cantoblanco, 28049 Madrid, Spain

Citation

This paper should be referenced as such :
Valdés-Mora, F ; Gòmez, del Pulgar T ; Lacal, JC
CDC42 (cell division cycle 42 (GTP binding protein, 25kDa))
Atlas Genet Cytogenet Oncol Haematol. 2009;13(11):804-811.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/CDC42ID40012ch1p36.html

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