Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

CDC25A (Cell division cycle 25A)

Written2008-02Dipankar Ray, Hiroaki Kiyokawa
Dept. of Mol. Pharmacol & Biol. Chem, Northwestern University, Chicago, IL 60611, USA (DR, HK); Robert H. Lurie Compre. Cancer Center, Northwestern University, Chicago, IL 60611, USA (HK)
Updated2015-08Christine Dozier, Stéphane Manenti
Cancer Research Center of Toulouse (CRCT), UMR1037 INSERM, ERL5294 CNRS, Université Toulouse III Paul Sabatier, Toulouse, France. christine.dozier@inserm.fr

Abstract CDC25A phosphatase is essential for cell cycle progression by activating the cyclin-associated kinases CDK4/6, CDK2 and CDK1. Its invalidation in mice is embryonic lethal. Its expression is tigthtly regulated at many levels and its overexpression is observed in various cancers, often associated with high grade tumors and poor prognosis.

Keywords CDC25, cell cycle, CDK/cyclin, apoptosis

(Note : for Links provided by Atlas : click)

Identity

Alias_namescell division cycle 25A
cell division cycle 25 homolog A (S. cerevisiae)
cell division cycle 25 homolog A (S. pombe)
Other aliasCDC25A2
HGNC (Hugo) CDC25A
LocusID (NCBI) 993
Atlas_Id 40004
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 48157178 and ends at 48188311 bp from pter ( according to hg19-Feb_2009)  [Mapping CDC25A.png]
Local_order The gene is located telomeric to CAMP (cathelicidin antimicrobial peptide) and centromeric to LOC729349 (a pseudogene similar to 60S ribosomal protein L17 (L23)). The gene starts at 48,173,672 bp from pter and ends at 48,204,805 bp from pter with a total size of 31,133 bases.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CDC25A (3p21.31) / CDC25A (3p21.31)CDC25A (3p21.31) / PAFAH1B2 (11q23.3)CDC25A (3p21.31) / PRKAR2A (3p21.31)
CDC25A (3p21.31) / SPINK8 (3p21.31)MAP4 (3p21.31) / CDC25A (3p21.31)

DNA/RNA

 
  Genomic organization of human CDC25A gene on chromosome 3 p-ter.
Description CDC25A is about 31.13 Kb located on the short (p) arm of chromosome 3, in the centromere-to-telomere orientation. The gene has 15 exons and the start codon is located at the end of exon 1 and stop codon in the beginning of exon 15.
Transcription The CDC25A transcript is 3704 bp in length. So far two major transcript variant have been reported, CDC25A1 and A2. The transcript variant CDC25A2, has a deletion of 120 nucleotides (exon 6) resulting in a protein having truncation of 40 amino acids (between amino acid 160-201). However, both the N-terminal and C-terminal end of the protein is the same in both splice variant.

Protein

 
  Domains of different isoforms of CDC25A (A1 and A2). The splice variant A2 lacks an in-frame exon (exon 6) encoding 40 amino acids (amino acid 160-201), however, has the same N- and C-termini compared to isoform A1. The approx. molecular weight of each isoform is mentioned in parenthesis.
Description The full length CDC25A protein consists of 524 amino acids with an estimated molecular weight of 59 kDa. The other reported isoform CDC25A2, consists of 484 amino acids with a molecular weight of 54.4 kDa (Wegener et al., 2000).. Both the isoforms have the same N- and C-terminal end, thus expected to have similar catalytic activity. The N-terminal regulatory domain contains several phosphorylation sites and shows low sequence homology between CDC25 family members, whereas C-terminal end has conserved Rhodanese homology domain containing the active site cysteine. The catalytic site contain the CX5R motif (C= cysteine; X= any amino acid; R= arginine) common to all protein tyrosine phosphatases (Boutros et al., 2006). Upon apoptosis induction, CDC25A is cleaved at D223 (D=Aspartic acid) by caspase to generate a catalytically active CDC25A C-terminal 37Kda protein (Mazars et al., 2009; Chou et al., 2010).
Expression CDC25A is expressed early during embryonic stages and in adults it is expressed in a variety of normal cells and tissues. CDC25A is a highly expressed gene in a variety of human cancers including breast, esophageal, gastric, lung, thyroid, head and neck cancers and also in high grade lymphomas.
Localisation CDC25A initially believed to be a nuclear protein. But using fluorescence loss in photobleaching (FLIP) a more dynamic nuclear-cytosolic shuttling of CDC25A localization has been reported. At the very N-terminus end between amino acid 38-59, the nuclear export sequence (NES) is located, whereas between amino acid 272-294, a bipartite nuclear localization signal (NLS) was proved to be important for its nuclear localization (Källström et al., 2005). Depending of the cell line, CDC25A is nuclear or nuclear and cytoplasmic.
Function - CDC25A is essential for early embryonic development as Cdc25A-null mice die in utero by embryonic day 7(Ray et al., 2007).
- It is a member of the M-phase inducer (MPI) phosphatase family protein, which not only regulates mitotic progression by activating mitotic CDKs in a dosage-dependent manner, it is also equally important in G1 and for G1 to S-phase transition.
- During G1, CDC25A dephosphorylates CDK4/CDK6 on tyrosine 17 and 24, respectively, allowing their association with D-type cyclins and thus their activation (Bertero et al., 2013). During G1 to S transition, it activates CDK2 by removing two inhibitory phosphates on residues threonine 14 and tyrosine 15. During G2/M transition CDC25A similarly regulates the activity of CDK1 (CDC2).
- It is an inhibitor of apoptosis by inhibiting apoptosis signal-regulating kinase 1 (ASK1). in a phosphatase-independent manner, by activating the AKT-survival pathway in the cytoplasm and also by stimulating NF-kB activity through NFKBIA (IκB- α) destabilization (review Fernandez-Vidal et al., 2008; review Shen and Huang, 2012; Hong et al., 2012). But overexpressed nuclear CDC25A also exhibits pro apoptotic activity by activating the pro-apoptotic factor FKHLR1 (review Fernandez-Vidal et al., 2008; review Shen and Huang, 2012).
- CDC25A plays an important role in spermatogenesis as decreased transcript level of Cdc25A is correlated with spermatogenic failure and failed sperm retrieval in infertile men. (Cheng et al., 2009).
-CDC25A also plays a role in meiotic maturation of oocytes, its activity is required for the metaphase II arrest in mouse oocytes (Oh et al., 2013).
- CDC25A was shown to function as a androgen receptor corepressor in prostate cancer cells (Chiu et al., 2009).
Regulation
- CDC25A is transcriptionally regulated by E2F, a transcription factor implicated at the G1/S transition, c-myc, STAT3, the p53-pathway via the transcription factor ATF3, TCF/beta-catenin, FOXM1, NANOG in embryonic stem cell and PROX1 in neural precursor (review Fernandez-Vidal et al., 2008; review Shen and Huang, 2012).
- CDC25A is also regulated at the translational level by the translation initiation factors EIF2S1 (eIF2alpha), EIF3M, the RNA-binding proteins BOLL in spermatogenesis, and various miRNAs such as let7b, 15a, 21, 449a, 449b, 483-3p, 424/503 cluster and 141-3p. Some of these miRNAs being deregulated in cancers can contribute to the overexpression of CDC25A in cancers.
- CDC25A activity can be regulated by phosphorylation events (review Fernandez-Vidal et al., 2008; review Shen and Huang, 2012). The kinases PIM-1, RAF1, CDK2, RSK, ROCK1 (p160Rock) and the phosphatase CDC14B have been shown to regulate CDC25A activity. The kinase CHK1 has been shown to phosphorylate CDC25A on serine 178 and threonine 507 preventing its interaction with its CDK/cyclin substrates.
- CDC25A is an unstable protein in interphase, or under several different stress conditions (DNA damage induced by ionizing radiation, ultraviolet light, replicative stress) being degraded by the proteasome after ubiquitination by SCFβTrCP E3 ubiquitin ligase. This ubiquitination is dependent on several phosphorylation events in the N-terminal part of the protein carried out by many kinases such as CHK1 (on serine 76, 124, 178, 279 and 293), CHK2 (on serine 124, 178 and 293), p38MAPK (on serine 76), GSK3-β (on serine 76), Plk3 (on threonine 80), NEK11 (on serine 82 and 88) and CK1alpha and epsilon (on serine 82) (review Fernandez-Vidal et al., 2008; review Shen and Huang, 2012).
- CDC25A protein is stabilized during mitosis due to phosphorylation on serine 18 and 116 by CDK1/cyclinB occuring at the G2/M transition (Mailand et al., 2002). At the mitotic exit and in early G1, CDC25A is degraded by the proteasome after ubiquitination by the E3 ubiquitine ligase APC/C (cyclosome) (review Fernandez-Vidal et al., 2008; review Shen and Huang, 2012).
- CDC25A protein level is important for oncogene-induced transformation and mouse mammary tumor virus (MMTV)-neu/ras induced mammary tumorigenesis (Ray et al., 2007).
- During early cell cycle progression glycogen synthase kinase 3-beta (GSK-3β) can phosphorylate allowing its proteasomal degradation. Interestingly, the same report showed that overproduction of CDC25A in some human cancers is correlated to the inactivation of GSK-3β (Kang et al., 2008).
- Overexpression of CDC25A in some human sarcomas has also been shown to be the result of transcriptional upregulation involving the transcription factor TCF/β-catenin upregulated upon activation of the wnt canonical signaling (Vijayakumar et al.,2011). HOMOLOGY CDC25A gene is highly conserved among mammals (99% homology with Chimpanzee; 90% with dog; about 86% with rat and about 85% with mouse). In mammals, CDC25A has two orthologs, CDC25B and CDC25C. Among them, the N-terminal regulatory region show low sequence homology (20-25% identity), however, the C-terminal catalytic region is quite conserved with about 64% homology with CDC25B and about 58% homology to CDC25C.

Mutations

Note Gene mutation or amplification is not commonly reported for CDC25A. A naturally occurring point mutation (C to A) of mouse Cdc25A gene has been reported where Histidine 128 (CAC) has been converted to Glutamine (CAA). This change caused an increase in CDC25A phosphatase activity and thereby affected erythropoiesis in mice only under certain genetic background (Melkun et al., 2002). A human polymorphism variant in which Serine 88 is converted to Phenylalanine has been described. This variant fails to interact with ASK1 and therefore does not suppress ASK1-mediated apoptosis, which leads to early embryonic lethality in mice and predisposes to cancer in human (Bahassi et al. 2011)..

Implicated in

Note
Note - CDC25A is overexpressed in a variety of human cancers including breast, hepatocellular, ovarian, colorectal, gastric, lung, thyroid, esophageal, laryngeal, head and neck cancers, retinoblastoma, glioma, and also in non-Hodgkin lymphoma. often associated with high grade tumours and bad prognosis (Boutros et al., 2007).
- Upregulation of CDC25A is also observed down-stream of the NPM1 / ALK oncogene in anaplastic large cell lymphoma and participates to their enhanced proliferation (Fernandez-Vidal et al., 2009). - CDC25A is overexpressed in erythroleukemia cell lines expressing the JAK2V617F oncogene, present in the majority of patients with polycythemia vera and one-half of those with essential thrombocythemia and primary myelofibrosis. This upregulation occurs at the translational level through the transcription factor STAT5 and the translational initiation factor eIF2alpha (Gautier et al., 2012).
- An upregulation of CDC25A activity due to its phosphorylation by deregulated CDK5 has been observed in Alzheimer's disease (Chang et al., 2012).
  
  
Entity Breast cancer
Note - In about 47% of early (T1) stage breast cancer patients CDC25A is reported to be overexpressed.
- In some breast cancer cell lines it was reported that CDC25A overexpression is mainly due to increased protein stability as oppose to gene amplification or transcriptional upregulation. (Löffler et al., 2003). In a subset of human breast cancers overexpression of the ubiquitin hydrolase DUB3, which deubiquitinates CDC25A preventing its degradation, is shown to be responsible for overexpression of CDC25A (Pereg et al., 2010).
- In mice, overexpression of CDC25A alone in mammary gland using mouse mammary tumor virus (MMTV) promoter, is not sufficient to induce mammary tumorigenesis. However, such mammary specific overexpression of CDC25A does cooperate with HER2/neu-ras signaling to form more aggressive tumors with enhanced genomic instability. (Ray et al., 2007).
- In contrast, hemizygous loss of Cdc25A in mice protected them significantly from MMTV-neu/ras-induced mammary tumorigenesis, possibly by restricting precancerous cell proliferation and also by enhancing G2-checkpoint response. Thus the protein level of CDC25A is crucial for the initiation and/or progression of breast tumorigenesis in mice (Ray and Kiyokawa, 2007).
Prognosis Overexpression of CDC25A is correlated with more aggressive breast cancer with poor prognosis.
Cytogenetics CDC25A overexpression in MMTV-CDC25A; MMTV-neu double transgenic mice caused faster tumor growth as compared to MMTV-neu single transgenic mice. Importantly, such CDC25A overexpressing tumor cells displayed miscoordination of S phase and mitosis, and had severe genomic instability as evidenced by aneuploidy and deletion of fragile chromosomal regions (e.g., telomeric region of chromosome 4, which is homologous to human chromosome 1p31-36, a hotspot for several human cancers including breast cancer).
  
  
Entity Hepatocellular carcinoma
Note Overexpression of CDC25A mRNAs was found in 69% of hepatocellular carcinomas (HCCs) and this overexpression was also confirmed by Immunohistochemistry (56% HCCs exhibit overexpression of CDC25A) and western blot analysis (Xu et al., 2003). Different CDC25 inhibitor (such as vitamin K analog Cpd 5; phenyl maleimide compound PM-20; 2-Methoxyestadiol, a physiological metabolite of estrogen) are capable of inhibiting the hepatocellular carcinoma growth both in vitro and in vivo (Wang et al., 2001; Kar et al, 2006).
Disease High expression of CDC25A was associated with dedifferentiated phenotype and portal vein invasion.
Prognosis CDC25A overexpression is associated with poor prognosis of hepatocellular carcinoma.
  
  
Entity Retinoblastoma
Note Overexpression of CDC25A mRNAs was found in 48,33 % retinoblastomas, confirmed by immunohistochemistry (52,29 %) and western blotting (Shingh et al., 2014).
Prognosis Expression of CDC25A showed significant correlation with poor tumour differentiation and tumour invasion.
  
  
Entity Non-Hodgkin's lymphoma
Prognosis High level of CDC25A mRNAs was found in 35 % of the tumors and were more frequently observed in aggressive than in indolent lymphomas. This was also confirmed at the protein level.
  
  
Entity Gastric cancer
Note By immunohistochemistry CDC25A was found expressed in 87.1 % of gastric carcinomas, correlated with c-myc overexpression (Xing et al., 2008).
Disease Overexpression of CDC25A was independent of intestinal or diffuse type of gastric cancer.
Prognosis Association between CDC25A expression and higher histological grade of differentiation.
  

Bibliography

A human cancer-predisposing polymorphism in Cdc25A is embryonic lethal in the mouse and promotes ASK-1 mediated apoptosis
Bahassi el M, Yin M, Robbins SB, Li YQ, Conrady DG, Yuan Z, Kovall RA, Herr AB, Stambrook PJ
Cell Div 2011 Feb 10;6(1):4
PMID 21310058
 
Mammalian G1- and S-phase checkpoints in response to DNA damage
Bartek J, Lukas J
Curr Opin Cell Biol 2001 Dec;13(6):738-47
PMID 11698191
 
CDC25A targeting by miR-483-3p decreases CCND-CDK4/6 assembly and contributes to cell cycle arrest
Bertero T, Gastaldi C, Bourget-Ponzio I, Mari B, Meneguzzi G, Barbry P, Ponzio G, Rezzonico R
Cell Death Differ 2013 Jun;20(6):800-11
PMID 23429262
 
The when and wheres of CDC25 phosphatases
Boutros R, Dozier C, Ducommun B
Curr Opin Cell Biol 2006 Apr;18(2):185-91
PMID 16488126
 
CDC25 phosphatases in cancer cells: key players? Good targets? Nat Rev Cancer
Boutros R, Lobjois V, Ducommun B
2007 Jul;7(7):495-507 Review
PMID 17568790
 
Deregulated Cdk5 triggers aberrant activation of cell cycle kinases and phosphatases inducing neuronal death
Chang KH, Vincent F, Shah K
J Cell Sci 2012 Nov 1;125(Pt 21):5124-37
PMID 22899714
 
Association of spermatogenic failure with decreased CDC25A expression in infertile men
Cheng YS, Kuo PL, Teng YN, Kuo TY, Chung CL, Lin YH, Liao RW, Lin JS, Lin YM
Hum Reprod 2006 Sep;21(9):2346-52
PMID 16720623
 
CDC25A functions as a novel Ar corepressor in prostate cancer cells
Chiu YT, Han HY, Leung SC, Yuen HF, Chau CW, Guo Z, Qiu Y, Chan KW, Wang X, Wong YC, Ling MT
J Mol Biol 2009 Jan 16;385(2):446-56
PMID 19013180
 
Pro-apoptotic role of Cdc25A: activation of cyclin B1/Cdc2 by the Cdc25A C-terminal domain
Chou ST, Yen YC, Lee CM, Chen MS
J Biol Chem 2010 Jun 4;285(23):17833-45
PMID 20368335
 
Chromosome mapping of human CDC25A and CDC25B phosphatases
Demetrick DJ, Beach DH
Genomics 1993 Oct;18(1):144-7
PMID 8276402
 
Upregulation of the CDC25A phosphatase down-stream of the NPM/ALK oncogene participates to anaplastic large cell lymphoma enhanced proliferation
Fernandez-Vidal A, Mazars A, Gautier EF, Prévost G, Payrastre B, Manenti S
Cell Cycle 2009 May 1;8(9):1373-9
PMID 19305144
 
Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins
Galaktionov K, Beach D
Cell 1991 Dec 20;67(6):1181-94
PMID 1836978
 
The cell cycle regulator CDC25A is a target for JAK2V617F oncogene
Gautier EF, Picard M, Laurent C, Marty C, Villeval JL, Demur C, Delhommeau F, Hexner E, Giraudier S, Bonnevialle N, Ducommun B, Récher C, Laurent G, Manenti S, Mansat-De Mas V
Blood 2012 Feb 2;119(5):1190-9
PMID 22065597
 
Cdc25A promotes cell survival by stimulating NF-B activity through I@kappa;B-@beta; phosphorylation and destabilization
Hong HY, Choi J, Cho YW, Kim BC
Biochem Biophys Res Commun 2012 Apr 6;420(2):293-6
PMID 22417828
 
Cdc25A localisation and shuttling: characterisation of sequences mediating nuclear export and import
Källströ H, Lindqvist A, Pospisil V, Lundgren A, Rosenthal CK
Exp Cell Res 2005 Feb 1;303(1):89-100
PMID 15572030
 
GSK-3 beta targets Cdc25A for ubiquitin-mediated proteolysis, and GSK-3 beta inactivation correlates with Cdc25A overproduction in human cancers
Kang T, Wei Y, Honaker Y, Yamaguchi H, Appella E, Hung MC, Piwnica-Worms H
Cancer Cell 2008 Jan;13(1):36-47
PMID 18167338
 
2-Methoxyestradiol inhibits hepatocellular carcinoma cell growth by inhibiting Cdc25 and inducing cell cycle arrest and apoptosis
Kar S, Wang M, Carr BI
Cancer Chemother Pharmacol 2008 Oct;62(5):831-40
PMID 18246350
 
Distinct modes of deregulation of the proto-oncogenic Cdc25A phosphatase in human breast cancer cell lines
Löffler H, Syljuåsen RG, Bartkova J, Worm J, Lukas J, Bartek J
Oncogene 2003 Nov 6;22(50):8063-71
PMID 14603247
 
Rapid destruction of human Cdc25A in response to DNA damage
Mailand N, Falck J, Lukas C, Syljuâsen RG, Welcker M, Bartek J, Lukas J
Science 2000 May 26;288(5470):1425-9
PMID 10827953
 
Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability
Mailand N, Podtelejnikov AV, Groth A, Mann M, Bartek J, Lukas J
EMBO J 2002 Nov 1;21(21):5911-20
PMID 12411508
 
A caspase-dependent cleavage of CDC25A generates an active fragment activating cyclin-dependent kinase 2 during apoptosis
Mazars A, Fernandez-Vidal A, Mondesert O, Lorenzo C, Prévost G, Ducommun B, Payrastre B, Racaud-Sultan C, Manenti S
Cell Death Differ 2009 Feb;16(2):208-18
PMID 18927589
 
A naturally occurring point substitution in Cdc25A, and not Fv2/Stk, is associated with altered cell-cycle status of early erythroid progenitor cells
Melkun E, Pilione M, Paulson RF
Blood 2002 Nov 15;100(10):3804-11
PMID 12411323
 
Cdc25A activity is required for the metaphase II arrest in mouse oocytes
Oh JS, Susor A, Schindler K, Schultz RM, Conti M
J Cell Sci 2013 Mar 1;126(Pt 5):1081-5
PMID 23345398
 
Ubiquitin hydrolase Dub3 promotes oncogenic transformation by stabilizing Cdc25A
Pereg Y, Liu BY, O'Rourke KM, Sagolla M, Dey A, Komuves L, French DM, Dixit VM
Nat Cell Biol 2010 Apr;12(4):400-6
PMID 20228808
 
CDC25A levels determine the balance of proliferation and checkpoint response
Ray D, Kiyokawa H
Cell Cycle 2007 Dec 15;6(24):3039-42
PMID 18073536
 
Hemizygous disruption of Cdc25A inhibits cellular transformation and mammary tumorigenesis in mice
Ray D, Terao Y, Nimbalkar D, Hirai H, Osmundson EC, Zou X, Franks R, Christov K, Kiyokawa H
Cancer Res 2007 Jul 15;67(14):6605-11
PMID 17638870
 
The role of Cdc25A in the regulation of cell proliferation and apoptosis
Shen T, Huang S
Anticancer Agents Med Chem 2012 Jul;12(6):631-9
PMID 22263797
 
Expression of CDC25A and CDC25B phosphatase proteins in human retinoblastoma and its correlation with clinicopathological parameters
Singh L, Pushker N, Sen S, Singh MK, Bakhshi S, Chawla B, Kashyap S
Br J Ophthalmol 2015 Apr;99(4):457-63
PMID 25326518
 
High-frequency canonical Wnt activation in multiple sarcoma subtypes drives proliferation through a TCF/-catenin target gene, CDC25A
Vijayakumar S, Liu G, Rus IA, Yao S, Chen Y, Akiri G, Grumolato L, Aaronson SA
Cancer Cell 2011 May 17;19(5):601-12
PMID 21575861
 
Involvement of Cdc25A phosphatase in Hep3B hepatoma cell growth inhibition induced by novel K vitamin analogs
Wang Z, Southwick EC, Wang M, Kar S, Rosi KS, Wilcox CS, Lazo JS, Carr BI
Cancer Res 2001 Oct 1;61(19):7211-6
PMID 11585757
 
Alternative splicing in the regulatory region of the human phosphatases CDC25A and CDC25C
Wegener S, Hampe W, Herrmann D, Schaller HC
Eur J Cell Biol 2000 Nov;79(11):810-5
PMID 11139144
 
Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents
Xiao Z, Chen Z, Gunasekera AH, Sowin TJ, Rosenberg SH, Fesik S, Zhang H
J Biol Chem 2003 Jun 13;278(24):21767-73
 
Expression of CDC25 phosphatases in human gastric cancer
Xing X, Chen J, Chen M
Dig Dis Sci 2008 Apr;53(4):949-53
PMID 17934831
 
Overexpression of CDC25A phosphatase is associated with hypergrowth activity and poor prognosis of human hepatocellular carcinomas
Xu X, Yamamoto H, Sakon M, Yasui M, Ngan CY, Fukunaga H, Morita T, Ogawa M, Nagano H, Nakamori S, Sekimoto M, Matsuura N, Monden M
Clin Cancer Res 2003 May;9(5):1764-72
PMID 12738732
 
The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1
Zou X, Tsutsui T, Ray D, Blomquist JF, Ichijo H, Ucker DS, Kiyokawa H
Mol Cell Biol 2001 Jul;21(14):4818-28
PMID 11416155
 

Citation

This paper should be referenced as such :
Dozier C, Manenti S
CDC25A (Cell division cycle 25A);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/CDC25AID40004ch3p21.html
History of this paper:
Ray, D ; Kiyokawa, H. CDC25A (cell division cycle 25A). Atlas Genet Cytogenet Oncol Haematol. 2008;12(6):421-424.
http://documents.irevues.inist.fr/bitstream/handle/2042/38593/02-2008-CDC25AID40004ch3p21.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(3;6)(q27;p21) PIM1/BCL6


External links

Nomenclature
HGNC (Hugo)CDC25A   1725
Cards
AtlasCDC25AID40004ch3p21
Entrez_Gene (NCBI)CDC25A  993  cell division cycle 25A
AliasesCDC25A2
GeneCards (Weizmann)CDC25A
Ensembl hg19 (Hinxton)ENSG00000164045 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000164045 [Gene_View]  chr3:48157178-48188311 [Contig_View]  CDC25A [Vega]
ICGC DataPortalENSG00000164045
TCGA cBioPortalCDC25A
AceView (NCBI)CDC25A
Genatlas (Paris)CDC25A
WikiGenes993
SOURCE (Princeton)CDC25A
Genetics Home Reference (NIH)CDC25A
Genomic and cartography
GoldenPath hg38 (UCSC)CDC25A  -     chr3:48157178-48188311 -  3p21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CDC25A  -     3p21.31   [Description]    (hg19-Feb_2009)
EnsemblCDC25A - 3p21.31 [CytoView hg19]  CDC25A - 3p21.31 [CytoView hg38]
Mapping of homologs : NCBICDC25A [Mapview hg19]  CDC25A [Mapview hg38]
OMIM116947   
Gene and transcription
Genbank (Entrez)AF277722 AI917350 AK290554 AY137580 BC007401
RefSeq transcript (Entrez)NM_001789 NM_201567
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CDC25A
Cluster EST : UnigeneHs.437705 [ NCBI ]
CGAP (NCI)Hs.437705
Alternative Splicing GalleryENSG00000164045
Gene ExpressionCDC25A [ NCBI-GEO ]   CDC25A [ EBI - ARRAY_EXPRESS ]   CDC25A [ SEEK ]   CDC25A [ MEM ]
Gene Expression Viewer (FireBrowse)CDC25A [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)993
GTEX Portal (Tissue expression)CDC25A
Human Protein AtlasENSG00000164045-CDC25A [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP30304   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP30304  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP30304
Splice isoforms : SwissVarP30304
Catalytic activity : Enzyme3.1.3.48 [ Enzyme-Expasy ]   3.1.3.483.1.3.48 [ IntEnz-EBI ]   3.1.3.48 [ BRENDA ]   3.1.3.48 [ KEGG ]   
PhosPhoSitePlusP30304
Domaine pattern : Prosite (Expaxy)RHODANESE_3 (PS50206)   
Domains : Interpro (EBI)MPI_Phosphatase    Rhodanese-like_dom   
Domain families : Pfam (Sanger)M-inducer_phosp (PF06617)    Rhodanese (PF00581)   
Domain families : Pfam (NCBI)pfam06617    pfam00581   
Domain families : Smart (EMBL)RHOD (SM00450)  
Conserved Domain (NCBI)CDC25A
DMDM Disease mutations993
Blocks (Seattle)CDC25A
PDB (SRS)1C25   
PDB (PDBSum)1C25   
PDB (IMB)1C25   
PDB (RSDB)1C25   
Structural Biology KnowledgeBase1C25   
SCOP (Structural Classification of Proteins)1C25   
CATH (Classification of proteins structures)1C25   
SuperfamilyP30304
Human Protein Atlas [tissue]ENSG00000164045-CDC25A [tissue]
Peptide AtlasP30304
HPRD00305
IPIIPI00220981   IPI00216430   IPI00925909   IPI00924949   
Protein Interaction databases
DIP (DOE-UCLA)P30304
IntAct (EBI)P30304
FunCoupENSG00000164045
BioGRIDCDC25A
STRING (EMBL)CDC25A
ZODIACCDC25A
Ontologies - Pathways
QuickGOP30304
Ontology : AmiGOregulation of cyclin-dependent protein serine/threonine kinase activity  G1/S transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  phosphoprotein phosphatase activity  protein tyrosine phosphatase activity  protein binding  nucleoplasm  cytosol  DNA replication  cell proliferation  response to radiation  protein deubiquitination  protein kinase binding  cellular response to UV  peptidyl-tyrosine dephosphorylation  chaperone binding  cell division  regulation of cell cycle  positive regulation of cell cycle G2/M phase transition  
Ontology : EGO-EBIregulation of cyclin-dependent protein serine/threonine kinase activity  G1/S transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  phosphoprotein phosphatase activity  protein tyrosine phosphatase activity  protein binding  nucleoplasm  cytosol  DNA replication  cell proliferation  response to radiation  protein deubiquitination  protein kinase binding  cellular response to UV  peptidyl-tyrosine dephosphorylation  chaperone binding  cell division  regulation of cell cycle  positive regulation of cell cycle G2/M phase transition  
Pathways : BIOCARTA [Genes]   
Pathways : KEGGCell cycle    Progesterone-mediated oocyte maturation    MicroRNAs in cancer   
REACTOMEP30304 [protein]
REACTOME PathwaysR-HSA-8862803 [pathway]   
NDEx NetworkCDC25A
Atlas of Cancer Signalling NetworkCDC25A
Wikipedia pathwaysCDC25A
Orthology - Evolution
OrthoDB993
GeneTree (enSembl)ENSG00000164045
Phylogenetic Trees/Animal Genes : TreeFamCDC25A
HOVERGENP30304
HOGENOMP30304
Homologs : HomoloGeneCDC25A
Homology/Alignments : Family Browser (UCSC)CDC25A
Gene fusions - Rearrangements
Fusion : MitelmanCDC25A/PRKAR2A [3p21.31/3p21.31]  
Fusion : MitelmanCDC25A/SPINK8 [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion : MitelmanMAP4/CDC25A [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion: TCGACDC25A 3p21.31 PRKAR2A 3p21.31 OV
Fusion: TCGACDC25A 3p21.31 SPINK8 3p21.31 LUSC
Fusion: TCGAMAP4 3p21.31 CDC25A 3p21.31 OV
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCDC25A [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CDC25A
dbVarCDC25A
ClinVarCDC25A
1000_GenomesCDC25A 
Exome Variant ServerCDC25A
ExAC (Exome Aggregation Consortium)ENSG00000164045
GNOMAD BrowserENSG00000164045
Genetic variants : HAPMAP993
Genomic Variants (DGV)CDC25A [DGVbeta]
DECIPHERCDC25A [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCDC25A 
Mutations
ICGC Data PortalCDC25A 
TCGA Data PortalCDC25A 
Broad Tumor PortalCDC25A
OASIS PortalCDC25A [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCDC25A  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCDC25A
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CDC25A
DgiDB (Drug Gene Interaction Database)CDC25A
DoCM (Curated mutations)CDC25A (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CDC25A (select a term)
intoGenCDC25A
NCG5 (London)CDC25A
Cancer3DCDC25A(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM116947   
Orphanet
MedgenCDC25A
Genetic Testing Registry CDC25A
NextProtP30304 [Medical]
TSGene993
GENETestsCDC25A
Target ValidationCDC25A
Huge Navigator CDC25A [HugePedia]
snp3D : Map Gene to Disease993
BioCentury BCIQCDC25A
ClinGenCDC25A
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD993
Chemical/Pharm GKB GenePA26259
Clinical trialCDC25A
Miscellaneous
canSAR (ICR)CDC25A (select the gene name)
Probes
Litterature
PubMed166 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCDC25A
EVEXCDC25A
GoPubMedCDC25A
iHOPCDC25A
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Oct 12 16:18:29 CEST 2017

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.