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

TPX2 (TPX2, microtubule-associated, homolog (Xenopus laevis))

Written2013-03Italia Anna Asteriti, Giulia Guarguaglini
Institute of Molecular Biology, Pathology, National Research, Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185, Rome, Italy

(Note : for Links provided by Atlas : click)

Identity

Alias_namesC20orf2
C20orf1
chromosome 20 open reading frame 1
TPX2, microtubule-associated, homolog (Xenopus laevis)
TPX2, microtubule-associated
Alias_symbol (synonym)p100
DIL-2
Other aliasDIL2
FLS353
GD:C20orf1
HCA519
HCTP4
REPP86
HGNC (Hugo) TPX2
LocusID (NCBI) 22974
Atlas_Id 42683
Location 20q11.21  [Link to chromosome band 20q11]
Location_base_pair Starts at 31739101 and ends at 31801800 bp from pter ( according to hg19-Feb_2009)  [Mapping TPX2.png]
Fusion genes
(updated 2016)
CMIP (16q23.2) / TPX2 (20q11.21)TM9SF4 (20q11.21) / TPX2 (20q11.21)TPX2 (20q11.21) / BCL2L1 (20q11.21)
TPX2 (20q11.21) / DEFB123 (20q11.21)TPX2 (20q11.21) / DUSP15 (20q11.21)TPX2 (20q11.21) / ERGIC1 (5q35.1)
TPX2 (20q11.21) / EYS (6q12)TPX2 (20q11.21) / HM13 (20q11.21)TPX2 (20q11.21) / RALY (20q11.22)
TPX2 (20q11.21) / REM1 (20q11.21)TPX2 (20q11.21) / UNC5D (8p12)

DNA/RNA

Description The TPX2 locus is on the q arm of chromosome 20; position 30326904 to 30389603, forward strand (NCBI, 22974).
Transcription The 3685 bp mRNA (NCBI Reference Sequence: NM_012112.4) contains 18 exons (16 coding); the processed cDNA is of 2244 bp. Ensembl reports the existence of a second transcript, containing 1 additional exon (ENST00000340513). TPX2 is expressed in proliferating cells; the TPX2 transcript was detected at high levels in human placenta, thymus and testis, while it was barely detectable in brain, heart, lung and pancreas (Manda et al., 1999; Wang et al., 2002; Satow et al., 2010).
Pseudogene No pseudogenes described in humans.

Protein

Description 747 aa; MW: 85653 Da.
Human TPX2 was initially identified as a nuclear protein of apparent molecular weight of 100 kDa expressed in proliferating cells, and named p100 (Heidebrecht et al., 1997); it was subsequently re-isolated in the search for mitotic targets of RanGTP as the homolog of X. laevis TPX2 (Gruss et al., 2001).
Human TPX2 harbours distinct functional domains:
- TPX2 is a microtubule-associated protein; both the full length protein and the N-terminus (amino acids 1-352) are able to bind microtubules in vitro (Schatz et al., 2003; Trieselmann et al., 2003). Additional regions in the C-terminus of TPX2 are involved in direct or indirect binding to microtubules in cells (Trieselmann et al., 2003). Domain characterisation of the Xenopus homolog also indicates the presence of one or more microtubule-binding domains in the N-terminus of TPX2; the C-terminal region has no direct affinity for microtubules but is required for localisation to spindle poles (Brunet et al., 2004).
- A non canonical nuclear localisation signal (NLS) centered around amino acids 314-315 (Schatz et al., 2003) mediates binding of TPX2 to importin alpha. Structural work has confirmed the association of the corresponding residues 284-287 in the Xenopus homolog protein to the "minor" NLS-binding site of importin alpha and has shown a second region (residues 327-330 of Xenopus TPX2) contacting the "major" NLS-binding site (Giesecke and Stewart, 2010).
- A KEN box (87-89) degradation motif is required for recognition by APC/CCdh1 (Stewart and Fang, 2005).
- The N-terminal region (residues 1-43; Bayliss et al., 2003) is required for the interaction with, and activation of, the Aurora-A kinase.
- An evolutionary conserved region of 35 amino acids at the C-terminus has been shown both in Xenopus and mouse TPX2 to bind the Eg5 kinesin (Eckerdt et al., 2008; Ma et al., 2010).
Expression TPX2 is expressed in a cell cycle-regulated manner; it appears in S phase and protein levels remain high in G2 and mitosis, until telophase when TPX2 is down-regulated via APC/CCdh1-dependent degradation (Heidebrecth et al., 1997; Gruss et al., 2001; Stewart and Fang, 2005). TPX2 is differentially expressed in tumor vs non-transformed cells (see below).
Localisation TPX2 localises to nuclei of interphase cells (S and G2); after nuclear envelope breakdown it associates with spindle microtubules; in late anaphase and telophase it also localises to the spindle mid-zone (Heidebrecht et al., 1997; Gruss et al., 2002; Garrett et al., 2002; figure 1).
 
  Figure 1. TPX2 localisation in human cells. Immunofluorescence images of U2OS osteosarcoma cells stained with DAPI (blue), anti-alpha-tubulin (green) and anti-TPX2 (red) antibodies show the nuclear localisation of TPX2 in interphase and TPX2 association to spindle microtubules in different mitotic stages. Scale bar: 10 μm.
Function Spindle assembly: TPX2 is a RanGTP-regulated spindle assembly factor (Gruss et al., 2001). An important contribution to the understanding of the mechanisms through which TPX2 acts in spindle assembly has been provided by studies that made use of the Xenopus egg extract system (Gruss and Vernos, 2004 and references therein).
Evidence obtained in mammalian cells support the notion that TPX2 plays a key role in spindle formation and function. Mitotic functions of TPX2 are negatively regulated by the binding to importin alpha and beta; the presence of RanGTP, by dissociating the complex between TPX2 and import receptors, induces the release of active TPX2 (Gruss et al., 2001). Indeed, excess TPX2 is able to rescue spindle pole organisation defects induced by importin beta overexpression in human cells (Ciciarello et al., 2004), pointing out the functional antagonism between TPX2 and import receptors in spindle assembly.
TPX2 acts in spindle organisation by:
i) its direct ability to induce microtubule assemblies and to bundle microtubules (Schatz et al., 2003);
ii) its targeting function: TPX2 recruits several mitotic regulators to the spindle, i.e. the Aurora-A kinase (Kufer et al., 2002), the kinesins hklp2 (Vanneste et al., 2009; Tanenbaum et al., 2009) and Eg5 (Ma et al., 2011b) and the scaffold attachment factor A (SAF-A; Ma et al., 2011a);
iii) regulation of specific mitotic factors: TPX2 interacts with the Aurora-A kinase and activates it, by stabilising it in the active conformation (Bayliss et al., 2003); in addition, TPX2 modulates Aurora-A protein stability, by counteracting proteasome-dependent Aurora-A degradation (Giubettini et al., 2011). TPX2 also regulates the activity of the Eg5 kinesin: in vitro assays show that TPX2 reduces the rate of Eg5-dependent microtubule gliding and microtubule-microtubule sliding (Ma et al., 2011).
Consistently, its inactivation in cultured mammalian cells impairs microtubule nucleation from chromosomes, and to a lesser extent from centrosomes, as well as organisation of microtubules within the spindle and cohesion of spindle poles (Garrett et al., 2002; Gruss et al., 2002; De Luca et al., 2006; Tulu et al., 2006; Bird and Hyman, 2008).
Neurogenesis in vertebrate brain: Neural progenitor cells in the apical-most region of the neuroepithelium, or ventricular zone, exhibit interkinetic nuclear migration (INM): their nuclei migrate apically in synchrony with cell cycle progression, so that mitosis occurs at the apical surface of the ventricular zone. TPX2 has been recently reported to promote interkinetic nuclear migration in mouse neural cells, by re-organising apical microtubules during the G2 phase (Kosodo et al., 2011).
DNA damage response (DDR): recent data show that TPX2 is involved in DDR to ionising radiations, by modulating the levels of γ-H2AX; TPX2 localises to DNA double strand breaks and interacts with DDR factors such as MDC1 (Neumayer et al., 2012). Previous data suggested a link between TPX2 and DDR: i) TPX2 is a putative substrate of the ATM/ATR kinases, as revealed in a large-scale proteomic screening (Matsuoka et al., 2007); ii) a functional interplay has been shown between Xenopus TPX2, the Aurora-A kinase and the p53 oncosuppressor (Pascreau et al., 2009).
Homology TPX2 orthologs have been identified in all classes of vertebrates, with Xenopus, mouse and human TPX2 being the best characterised. TPX2-like proteins have been described in plants (Vos et al., 2008; Evrard et al., 2009), C. elegans (Ozlü et al., 2005) and Drosophila melanogaster (Goshima, 2011).

Implicated in

Note
  
Entity Various cancers
Oncogenesis The TPX2 gene is located on the long arm of chromosome 20, in a region that is frequently amplified in cancer. Growing evidence, described in detail in sections below, indicate that TPX2 levels are increased in tumors and suggest that TPX2 is involved in tumorigenesis. An overall evaluation of TPX2 overexpression in different cancer types can be obtained with the Oncomine database (www.oncomine.org), which collects data from several microarrays; a recent study using Oncomine shows that TPX2 is significantly overexpressed in about 25% of analyses of tumor vs normal tissues and that it ranks among the first 10% overexpressed genes in the vast majority of cases (Asteriti et al., 2010).
Association of increased TPX2 levels, chromosomal instability (CIN) and cancer has also been highlighted: TPX2 ranked first in a CIN25 signature, the overexpression of which is predictive of poor clinical outcome (Carter et al., 2006). A TPX2 gene signature has also been recently identified as associated with metastatic progression in breast cancer (Hu et al., 2012).
  
  
Entity Brain cancer
Prognosis Analysis of astrocytoma tissue samples showed positive TPX2 staining, while TPX2 was not detected in normal brain tissues; in addition, TPX2 expression levels were higher in high-grade, compared with low-grade, astrocytomas. The median survival of patients correlated with TPX2 levels, with high TPX2 being associated with overall poor survival (Li et al., 2010). TPX2 was also identified among 9 genes which are significantly overexpressed in grade III vs grade I meningiomas (Stuart et al., 2011) and among 14 genes with elevated expression in high-risk neuroblastomas with 1p loss and MYCN amplification (Ooi et al., 2012).
  
  
Entity Oral squamous cell carcinoma
Prognosis Expression levels of TPX2 were not related with tumor size, lymph node invasion or histopathologic grading (Fenner et al., 2005).
Oncogenesis TPX2 expression levels, analysed by RT-PCR (Shigeishi et al., 2009a) or immunohistochemistry (Fenner et al., 2005), were significantly higher compared with normal oral tissues.
  
  
Entity Salivary gland carcinoma
Oncogenesis Levels of TPX2 mRNA were analysed by RT-PCR in 20 human salivary gland carcinomas compared with 6 normal submandibular glands and resulted higher in all tumor samples (Shigeishi et al., 2009b).
  
  
Entity Lung cancer
Note Human bronchial epithelial cells malignantly transformed by anti-BPDE (16HBE-C) displayed abnormal levels of phosphorylated TPX2 on tyrosine residues (Zhang et al., 2008).
Prognosis Three studies indicate the prognostic value of TPX2 overexpression in adenocarcinomas (Kadara et al., 2009; Li et al., 2013) and squamous cell carcinoma (Ma et al., 2006): TPX2 expression is associated with tumor grade and stage and poor survival rates. In particular, TPX2 is among the top genes in prognostic signatures identified as classifiers for overall survival of patients (Kadara et al., 2009; Li et al. 2013).
Oncogenesis Several studies report increased TPX2 expression levels in primary lung tumors (adenocarcinomas, squamous cell carcinoma, small cell carcinoma) and lung cancer cell lines, compared to controls (Manda et al., 1999; Tonon et al., 2005; Ma et al., 2006; Zhang et al., 2008; Kadara et al., 2009; Li et al., 2013).
  
  
Entity Colon cancer
Oncogenesis TPX2 overexpression in colorectal cancer was observed by suppression subtractive hybridisation (SSH) method applied to a primary stage III rectal adenocarcinoma and the matched non-neoplastic mucosa (Hufton et al., 1999). In addition, protein levels of TPX2 and of its partner Aurora-A correlate significantly with chromosome 20q DNA copy number status: TPX2 and Aurora-A are therefore implicated in the 20q amplicon-driven progression of colorectal adenoma to carcinoma (Sillars-Hardebol et al., 2012).
  
  
Entity Liver cancer
Oncogenesis The TPX2 transcript is expressed at high levels in hepatocellular carcinomas, compared with weak expression in paired normal tissues (Wang et al., 2002; Satow et al., 2010).
  
  
Entity Pancreatic cancer
Prognosis Increased expression of TPX2 was associated with poor survival and significantly correlated with histological grade in two independent cohorts (from Germany and Maryland; Zhang et al., 2012). When cohorts were combined, and stratified by resection margin status (positive vs negative), TPX2 was associated with cancer-specific mortality in resection margin-positive patients and with prognosis in resection margin-negative patients.
Oncogenesis Low copy-number amplification of TPX2, associated with increased mRNA and protein levels, was observed in pancreatic cancer cell lines (Warner et al., 2009); the TPX2 gene is also included in an amplicon identified by microarray analysis of pancreatic ductal adenocarcinoma (Tonon et al., 2005). Immunohistochemical staining of tissue microarrays showed increased TPX2 levels in pancreatic tumors compared with the normal counterparts (Warner et al., 2009; Zhang et al., 2012).
  
  
Entity Ovarian cancer
Note The Aurora-A kinase, which interacts with, and is regulated by, TPX2 is also differentially expressed in ovarian carcinomas vs adenomas (Scharer et al., 2008).
Prognosis A comparative analysis revealed a stronger (15 to 27 fold) overexpression of TPX2 in primary ovarian carcinomas compared with non-malignant adenomas (Scharer et al., 2008).
Oncogenesis A high resolution genome wide copy number analysis combined with matching expression data from primary epithelial ovarian carcinomas of various histotypes showed that TPX2 is among the most significantly differentially expressed genes in a chromosome 20 region frequently amplified in ovarian cancer (Ramakrishna et al., 2010).
  
  
Entity Cervical cancer
Prognosis TPX2 expression levels in cervical squamous cell carcinoma positively correlate with tumor stage and grade, and lymph node metastasis (Chang et al., 2012).
Oncogenesis Copy number increase of chromosome 20q, where the TPX2 gene is located, is frequently observed in cervical cancers; indeed TPX2 is reported among the 26 genes that are significantly overexpressed as consequence of 20q gain (Scotto et al., 2008). TPX2 mRNA and protein are highly expressed in cervical cancer, while its expression is almost absent in normal cervical tissues (Chang et al., 2012).
  
  
Entity Bladder cancer
Oncogenesis RNA microarrays and RT-PCR analyses showed significant upregulation of TPX2 in urothelial carcinomas of the bladder compared with normal urothelium (Zhou et al., 2013).
  
  
Entity Mesothelial tumors
Prognosis Immunostaining of malignant mesothelioma samples compared to benign reactive mesothelial hyperplasia showed significant overexpression of TPX2 in malignant samples, suggesting that TPX2 represents a useful marker in this respect (Taheri et al., 2008).
  

To be noted

Growing evidence highlights the therapeutic potential of TPX2 inactivation. Two RNAi-based screenings identified TPX2 among essential genes for tumor survival and hence the most promising target candidates for anti-cancer strategies (Morgan-Lappe et al., 2007; Martens-de Kemp et al., 2013). Several studies provide direct demonstration of the anti-proliferative effects of TPX2 inactivation in cancer cells of different tumor types (Morgan-Lappe et al., 2007; Zhang et al., 2008; Warner et al., 2009; Li et al., 2010; Satow et al., 2010; Chang et al., 2012; Vainio et al., 2012; Martens-de Kemp et al., 2013). In addition, TPX2 inactivation significantly reduced tumor growth in xenografts models based on inoculation in nude mice of pancreatic or hepatocellular carcinoma cells (Warner et al., 2009; Satow et al., 2010).

Bibliography

The Aurora-A/TPX2 complex: a novel oncogenic holoenzyme?
Asteriti IA, Rensen WM, Lindon C, Lavia P, Guarguaglini G.
Biochim Biophys Acta. 2010 Dec;1806(2):230-9. doi: 10.1016/j.bbcan.2010.08.001. Epub 2010 Aug 12. (REVIEW)
PMID 20708655
 
Structural basis of Aurora-A activation by TPX2 at the mitotic spindle.
Bayliss R, Sardon T, Vernos I, Conti E.
Mol Cell. 2003 Oct;12(4):851-62.
PMID 14580337
 
Building a spindle of the correct length in human cells requires the interaction between TPX2 and Aurora A.
Bird AW, Hyman AA.
J Cell Biol. 2008 Jul 28;182(2):289-300. doi: 10.1083/jcb.200802005.
PMID 18663142
 
Characterization of the TPX2 domains involved in microtubule nucleation and spindle assembly in Xenopus egg extracts.
Brunet S, Sardon T, Zimmerman T, Wittmann T, Pepperkok R, Karsenti E, Vernos I.
Mol Biol Cell. 2004 Dec;15(12):5318-28. Epub 2004 Sep 22.
PMID 15385625
 
A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers.
Carter SL, Eklund AC, Kohane IS, Harris LN, Szallasi Z.
Nat Genet. 2006 Sep;38(9):1043-8. Epub 2006 Aug 20.
PMID 16921376
 
The TPX2 gene is a promising diagnostic and therapeutic target for cervical cancer.
Chang H, Wang J, Tian Y, Xu J, Gou X, Cheng J.
Oncol Rep. 2012 May;27(5):1353-9. doi: 10.3892/or.2012.1668. Epub 2012 Feb 1.
PMID 22307108
 
Importin beta is transported to spindle poles during mitosis and regulates Ran-dependent spindle assembly factors in mammalian cells.
Ciciarello M, Mangiacasale R, Thibier C, Guarguaglini G, Marchetti E, Di Fiore B, Lavia P.
J Cell Sci. 2004 Dec 15;117(Pt 26):6511-22. Epub 2004 Nov 30.
PMID 15572412
 
A functional interplay between Aurora-A, Plk1 and TPX2 at spindle poles: Plk1 controls centrosomal localization of Aurora-A and TPX2 spindle association.
De Luca M, Lavia P, Guarguaglini G.
Cell Cycle. 2006 Feb;5(3):296-303. Epub 2006 Feb 7.
PMID 16418575
 
Spindle pole regulation by a discrete Eg5-interacting domain in TPX2.
Eckerdt F, Eyers PA, Lewellyn AL, Prigent C, Maller JL.
Curr Biol. 2008 Apr 8;18(7):519-25. doi: 10.1016/j.cub.2008.02.077. Epub 2008 Mar 27.
PMID 18372177
 
Plant TPX2 and related proteins.
Evrard JL, Pieuchot L, Vos JW, Vernos I, Schmit AC.
Plant Signal Behav. 2009 Jan;4(1):69-72.
PMID 19704713
 
Restricted-expressed proliferation-associated protein (Repp86) expression in squamous cell carcinoma of the oral cavity.
Fenner M, Wehrhan F, Jehle M, Amann K, Radespiel-Troger M, Grabenbauer G, Zenk J, Nkenke E, Schinhammer M, Schultze-Mosgau S.
Strahlenther Onkol. 2005 Dec;181(12):755-61.
PMID 16362784
 
hTPX2 is required for normal spindle morphology and centrosome integrity during vertebrate cell division.
Garrett S, Auer K, Compton DA, Kapoor TM.
Curr Biol. 2002 Dec 10;12(23):2055-9.
PMID 12477396
 
Novel binding of the mitotic regulator TPX2 (target protein for Xenopus kinesin-like protein 2) to importin-alpha.
Giesecke A, Stewart M.
J Biol Chem. 2010 Jun 4;285(23):17628-35. doi: 10.1074/jbc.M110.102343. Epub 2010 Mar 23.
PMID 20335181
 
Control of Aurora-A stability through interaction with TPX2.
Giubettini M, Asteriti IA, Scrofani J, De Luca M, Lindon C, Lavia P, Guarguaglini G.
J Cell Sci. 2011 Jan 1;124(Pt 1):113-22. doi: 10.1242/jcs.075457. Epub 2010 Dec 8.
PMID 21147853
 
Identification of a TPX2-like microtubule-associated protein in Drosophila.
Goshima G.
PLoS One. 2011;6(11):e28120. doi: 10.1371/journal.pone.0028120. Epub 2011 Nov 30.
PMID 22140519
 
Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity.
Gruss OJ, Carazo-Salas RE, Schatz CA, Guarguaglini G, Kast J, Wilm M, Le Bot N, Vernos I, Karsenti E, Mattaj IW.
Cell. 2001 Jan 12;104(1):83-93.
PMID 11163242
 
The mechanism of spindle assembly: functions of Ran and its target TPX2.
Gruss OJ, Vernos I.
J Cell Biol. 2004 Sep 27;166(7):949-55. (REVIEW)
PMID 15452138
 
Chromosome-induced microtubule assembly mediated by TPX2 is required for spindle formation in HeLa cells.
Gruss OJ, Wittmann M, Yokoyama H, Pepperkok R, Kufer T, Sillje H, Karsenti E, Mattaj IW, Vernos I.
Nat Cell Biol. 2002 Nov;4(11):871-9.
PMID 12389033
 
p100: a novel proliferation-associated nuclear protein specifically restricted to cell cycle phases S, G2, and M.
Heidebrecht HJ, Buck F, Steinmann J, Sprenger R, Wacker HH, Parwaresch R.
Blood. 1997 Jul 1;90(1):226-33.
PMID 9207457
 
Integrated cross-species transcriptional network analysis of metastatic susceptibility.
Hu Y, Wu G, Rusch M, Lukes L, Buetow KH, Zhang J, Hunter KW.
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3184-9. doi: 10.1073/pnas.1117872109. Epub 2012 Jan 30.
PMID 22308418
 
A profile of differentially expressed genes in primary colorectal cancer using suppression subtractive hybridization.
Hufton SE, Moerkerk PT, Brandwijk R, de Bruine AP, Arends JW, Hoogenboom HR.
FEBS Lett. 1999 Dec 10;463(1-2):77-82.
PMID 10601642
 
Identification of gene signatures and molecular markers for human lung cancer prognosis using an in vitro lung carcinogenesis system.
Kadara H, Lacroix L, Behrens C, Solis L, Gu X, Lee JJ, Tahara E, Lotan D, Hong WK, Wistuba II, Lotan R.
Cancer Prev Res (Phila). 2009 Aug;2(8):702-11. doi: 10.1158/1940-6207.CAPR-09-0084. Epub 2009 Jul 28.
PMID 19638491
 
Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain.
Kosodo Y, Suetsugu T, Suda M, Mimori-Kiyosue Y, Toida K, Baba SA, Kimura A, Matsuzaki F.
EMBO J. 2011 May 4;30(9):1690-704. doi: 10.1038/emboj.2011.81. Epub 2011 Mar 25.
PMID 21441895
 
Human TPX2 is required for targeting Aurora-A kinase to the spindle.
Kufer TA, Sillje HH, Korner R, Gruss OJ, Meraldi P, Nigg EA.
J Cell Biol. 2002 Aug 19;158(4):617-23. Epub 2002 Aug 12.
PMID 12177045
 
Expression of targeting protein for Xenopus kinesin-like protein 2 is associated with progression of human malignant astrocytoma.
Li B, Qi XQ, Chen X, Huang X, Liu GY, Chen HR, Huang CG, Luo C, Lu YC.
Brain Res. 2010 Sep 17;1352:200-7. doi: 10.1016/j.brainres.2010.06.060. Epub 2010 Jun 30.
PMID 20599806
 
Network-based approach identified cell cycle genes as predictor of overall survival in lung adenocarcinoma patients.
Li Y, Tang H, Sun Z, Bungum AO, Edell ES, Lingle WL, Stoddard SM, Zhang M, Jen J, Yang P, Wang L.
Lung Cancer. 2013 Apr;80(1):91-8. doi: 10.1016/j.lungcan.2012.12.022. Epub 2013 Jan 26.
PMID 23357462
 
The nuclear scaffold protein SAF-A is required for kinetochore-microtubule attachment and contributes to the targeting of Aurora-A to mitotic spindles.
Ma N, Matsunaga S, Morimoto A, Sakashita G, Urano T, Uchiyama S, Fukui K.
J Cell Sci. 2011a Feb 1;124(Pt 3):394-404. doi: 10.1242/jcs.063347.
PMID 21242313
 
TPX2 regulates the localization and activity of Eg5 in the mammalian mitotic spindle.
Ma N, Titus J, Gable A, Ross JL, Wadsworth P.
J Cell Biol. 2011b Oct 3;195(1):87-98. doi: 10.1083/jcb.201106149.
PMID 21969468
 
Poleward transport of TPX2 in the mammalian mitotic spindle requires dynein, Eg5, and microtubule flux.
Ma N, Tulu US, Ferenz NP, Fagerstrom C, Wilde A, Wadsworth P.
Mol Biol Cell. 2010 Mar 15;21(6):979-88. doi: 10.1091/mbc.E09-07-0601. Epub 2010 Jan 28.
PMID 20110350
 
Expression of targeting protein for xklp2 associated with both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer.
Ma Y, Lin D, Sun W, Xiao T, Yuan J, Han N, Guo S, Feng X, Su K, Mao Y, Cheng S, Gao Y.
Clin Cancer Res. 2006 Feb 15;12(4):1121-7.
PMID 16489064
 
Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display.
Manda R, Kohno T, Matsuno Y, Takenoshita S, Kuwano H, Yokota J.
Genomics. 1999 Oct 1;61(1):5-14.
PMID 10512675
 
Functional genetic screens identify genes essential for tumor cell survival in head and neck and lung cancer.
Martens-de Kemp SR, Nagel R, Stigter-van Walsum M, van der Meulen IH, van Beusechem VW, Braakhuis BJ, Brakenhoff RH.
Clin Cancer Res. 2013 Apr 15;19(8):1994-2003. doi: 10.1158/1078-0432.CCR-12-2539. Epub 2013 Feb 26.
PMID 23444224
 
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ.
Science. 2007 May 25;316(5828):1160-6.
PMID 17525332
 
Identification of Ras-related nuclear protein, targeting protein for xenopus kinesin-like protein 2, and stearoyl-CoA desaturase 1 as promising cancer targets from an RNAi-based screen.
Morgan-Lappe SE, Tucker LA, Huang X, Zhang Q, Sarthy AV, Zakula D, Vernetti L, Schurdak M, Wang J, Fesik SW.
Cancer Res. 2007 May 1;67(9):4390-8.
PMID 17483353
 
Targeting protein for xenopus kinesin-like protein 2 (TPX2) regulates ?-histone 2AX (?-H2AX) levels upon ionizing radiation.
Neumayer G, Helfricht A, Shim SY, Le HT, Lundin C, Belzil C, Chansard M, Yu Y, Lees-Miller SP, Gruss OJ, van Attikum H, Helleday T, Nguyen MD.
J Biol Chem. 2012 Dec 7;287(50):42206-22. doi: 10.1074/jbc.M112.385674. Epub 2012 Oct 8.
PMID 23045526
 
Segmental chromosome aberrations converge on overexpression of mitotic spindle regulatory genes in high-risk neuroblastoma.
Ooi WF, Re A, Sidarovich V, Canella V, Arseni N, Adami V, Guarguaglini G, Giubettini M, Scaruffi P, Stigliani S, Lavia P, Tonini GP, Quattrone A.
Genes Chromosomes Cancer. 2012 Jun;51(6):545-56. doi: 10.1002/gcc.21940. Epub 2012 Feb 15.
PMID 22337647
 
An essential function of the C. elegans ortholog of TPX2 is to localize activated aurora A kinase to mitotic spindles.
Ozlu N, Srayko M, Kinoshita K, Habermann B, O'toole ET, Muller-Reichert T, Schmalz N, Desai A, Hyman AA.
Dev Cell. 2005 Aug;9(2):237-48.
PMID 16054030
 
Phosphorylation of p53 is regulated by TPX2-Aurora A in xenopus oocytes.
Pascreau G, Eckerdt F, Lewellyn AL, Prigent C, Maller JL.
J Biol Chem. 2009 Feb 27;284(9):5497-505. doi: 10.1074/jbc.M805959200. Epub 2009 Jan 2.
PMID 19121998
 
Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.
Ramakrishna M, Williams LH, Boyle SE, Bearfoot JL, Sridhar A, Speed TP, Gorringe KL, Campbell IG.
PLoS One. 2010 Apr 8;5(4):e9983. doi: 10.1371/journal.pone.0009983.
PMID 20386695
 
Combined functional genome survey of therapeutic targets for hepatocellular carcinoma.
Satow R, Shitashige M, Kanai Y, Takeshita F, Ojima H, Jigami T, Honda K, Kosuge T, Ochiya T, Hirohashi S, Yamada T.
Clin Cancer Res. 2010 May 1;16(9):2518-28. doi: 10.1158/1078-0432.CCR-09-2214. Epub 2010 Apr 13.
PMID 20388846
 
Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells.
Scharer CD, Laycock N, Osunkoya AO, Logani S, McDonald JF, Benigno BB, Moreno CS.
J Transl Med. 2008 Dec 11;6:79. doi: 10.1186/1479-5876-6-79.
PMID 19077237
 
Importin alpha-regulated nucleation of microtubules by TPX2.
Schatz CA, Santarella R, Hoenger A, Karsenti E, Mattaj IW, Gruss OJ, Carazo-Salas RE.
EMBO J. 2003 May 1;22(9):2060-70.
PMID 12727873
 
Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression.
Scotto L, Narayan G, Nandula SV, Arias-Pulido H, Subramaniyam S, Schneider A, Kaufmann AM, Wright JD, Pothuri B, Mansukhani M, Murty VV.
Genes Chromosomes Cancer. 2008 Sep;47(9):755-65. doi: 10.1002/gcc.20577.
PMID 18506748
 
Expression of TPX2 in salivary gland carcinomas.
Shigeishi H, Ohta K, Hiraoka M, Fujimoto S, Minami M, Higashikawa K, Kamata N.
Oncol Rep. 2009b Feb;21(2):341-4.
PMID 19148505
 
TPX2 and AURKA promote 20q amplicon-driven colorectal adenoma to carcinoma progression.
Sillars-Hardebol AH, Carvalho B, Tijssen M, Belien JA, de Wit M, Delis-van Diemen PM, Ponten F, van de Wiel MA, Fijneman RJ, Meijer GA.
Gut. 2012 Nov;61(11):1568-75. Epub 2011 Dec 29.
PMID 22207630
 
Anaphase-promoting complex/cyclosome controls the stability of TPX2 during mitotic exit.
Stewart S, Fang G.
Mol Cell Biol. 2005 Dec;25(23):10516-27.
PMID 16287863
 
Identification of gene markers associated with aggressive meningioma by filtering across multiple sets of gene expression arrays.
Stuart JE, Lusis EA, Scheck AC, Coons SW, Lal A, Perry A, Gutmann DH.
J Neuropathol Exp Neurol. 2011 Jan;70(1):1-12. doi: 10.1097/NEN.0b013e3182018f1c.
PMID 21157382
 
The diagnostic value of Ki-67 and repp86 in distinguishing between benign and malignant mesothelial proliferations.
Taheri ZM, Mehrafza M, Mohammadi F, Khoddami M, Bahadori M, Masjedi MR.
Arch Pathol Lab Med. 2008 Apr;132(4):694-7. doi: 10.1043/1543-2165(2008)132[694:TDVOKA]2.0.CO;2.
PMID 18384222
 
Kif15 cooperates with eg5 to promote bipolar spindle assembly.
Tanenbaum ME, Macurek L, Janssen A, Geers EF, Alvarez-Fernandez M, Medema RH.
Curr Biol. 2009 Nov 3;19(20):1703-11. doi: 10.1016/j.cub.2009.08.027. Epub 2009 Oct 8.
PMID 19818618
 
High-resolution genomic profiles of human lung cancer.
Tonon G, Wong KK, Maulik G, Brennan C, Feng B, Zhang Y, Khatry DB, Protopopov A, You MJ, Aguirre AJ, Martin ES, Yang Z, Ji H, Chin L, Depinho RA.
Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9625-30. Epub 2005 Jun 27.
PMID 15983384
 
Ran modulates spindle assembly by regulating a subset of TPX2 and Kid activities including Aurora A activation.
Trieselmann N, Armstrong S, Rauw J, Wilde A.
J Cell Sci. 2003 Dec 1;116(Pt 23):4791-8.
PMID 14600264
 
Molecular requirements for kinetochore-associated microtubule formation in mammalian cells.
Tulu US, Fagerstrom C, Ferenz NP, Wadsworth P.
Curr Biol. 2006 Mar 7;16(5):536-41.
PMID 16527751
 
High-throughput transcriptomic and RNAi analysis identifies AIM1, ERGIC1, TMED3 and TPX2 as potential drug targets in prostate cancer.
Vainio P, Mpindi JP, Kohonen P, Fey V, Mirtti T, Alanen KA, Perala M, Kallioniemi O, Iljin K.
PLoS One. 2012;7(6):e39801. doi: 10.1371/journal.pone.0039801. Epub 2012 Jun 28.
PMID 22761906
 
The role of Hklp2 in the stabilization and maintenance of spindle bipolarity.
Vanneste D, Takagi M, Imamoto N, Vernos I.
Curr Biol. 2009 Nov 3;19(20):1712-7. doi: 10.1016/j.cub.2009.09.019. Epub 2009 Oct 8.
PMID 19818619
 
The plant TPX2 protein regulates prospindle assembly before nuclear envelope breakdown.
Vos JW, Pieuchot L, Evrard JL, Janski N, Bergdoll M, de Ronde D, Perez LH, Sardon T, Vernos I, Schmit AC.
Plant Cell. 2008 Oct;20(10):2783-97. doi: 10.1105/tpc.107.056796. Epub 2008 Oct 21.
PMID 18941054
 
Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies.
Wang Y, Han KJ, Pang XW, Vaughan HA, Qu W, Dong XY, Peng JR, Zhao HT, Rui JA, Leng XS, Cebon J, Burgess AW, Chen WF.
J Immunol. 2002 Jul 15;169(2):1102-9.
PMID 12097419
 
Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells.
Warner SL, Stephens BJ, Nwokenkwo S, Hostetter G, Sugeng A, Hidalgo M, Trent JM, Han H, Von Hoff DD.
Clin Cancer Res. 2009 Nov 1;15(21):6519-28. doi: 10.1158/1078-0432.CCR-09-0077. Epub 2009 Oct 27.
PMID 19861455
 
DPEP1 inhibits tumor cell invasiveness, enhances chemosensitivity and predicts clinical outcome in pancreatic ductal adenocarcinoma.
Zhang G, Schetter A, He P, Funamizu N, Gaedcke J, Ghadimi BM, Ried T, Hassan R, Yfantis HG, Lee DH, Lacy C, Maitra A, Hanna N, Alexander HR, Hussain SP.
PLoS One. 2012;7(2):e31507. doi: 10.1371/journal.pone.0031507. Epub 2012 Feb 20.
PMID 22363658
 
TPX2 in malignantly transformed human bronchial epithelial cells by anti-benzo[a]pyrene-7,8-diol-9,10-epoxide.
Zhang L, Huang H, Deng L, Chu M, Xu L, Fu J, Zhu Y, Zhang X, Liu S, Zhou Z, Wang Y.
Toxicology. 2008 Oct 30;252(1-3):49-55. doi: 10.1016/j.tox.2008.07.059. Epub 2008 Aug 3.
PMID 18723071
 
The investigational Aurora kinase A inhibitor MLN8237 induces defects in cell viability and cell-cycle progression in malignant bladder cancer cells in vitro and in vivo.
Zhou N, Singh K, Mir MC, Parker Y, Lindner D, Dreicer R, Ecsedy JA, Zhang Z, Teh BT, Almasan A, Hansel DE.
Clin Cancer Res. 2013 Apr 1;19(7):1717-28. doi: 10.1158/1078-0432.CCR-12-2383. Epub 2013 Feb 12.
PMID 23403633
 

Citation

This paper should be referenced as such :
Asteriti, IA ; Guarguaglini, G
TPX2 (TPX2, microtubule-associated, homolog (Xenopus laevis))
Atlas Genet Cytogenet Oncol Haematol. 2013;17(9):623-629.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TPX2ID42683ch20q11.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Lung: Translocations in Small Cell Carcinoma


External links

Nomenclature
HGNC (Hugo)TPX2   1249
Cards
AtlasTPX2ID42683ch20q11
Entrez_Gene (NCBI)TPX2  22974  TPX2, microtubule nucleation factor
AliasesC20orf1; C20orf2; DIL-2; DIL2; 
FLS353; GD:C20orf1; HCA519; HCTP4; REPP86; p100
GeneCards (Weizmann)TPX2
Ensembl hg19 (Hinxton)ENSG00000088325 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000088325 [Gene_View]  chr20:31739101-31801800 [Contig_View]  TPX2 [Vega]
ICGC DataPortalENSG00000088325
TCGA cBioPortalTPX2
AceView (NCBI)TPX2
Genatlas (Paris)TPX2
WikiGenes22974
SOURCE (Princeton)TPX2
Genetics Home Reference (NIH)TPX2
Genomic and cartography
GoldenPath hg38 (UCSC)TPX2  -     chr20:31739101-31801800 +  20q11.21   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TPX2  -     20q11.21   [Description]    (hg19-Feb_2009)
EnsemblTPX2 - 20q11.21 [CytoView hg19]  TPX2 - 20q11.21 [CytoView hg38]
Mapping of homologs : NCBITPX2 [Mapview hg19]  TPX2 [Mapview hg38]
OMIM605917   
Gene and transcription
Genbank (Entrez)AB024704 AB027467 AF098158 AF146731 AF244547
RefSeq transcript (Entrez)NM_012112
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)TPX2
Cluster EST : UnigeneHs.244580 [ NCBI ]
CGAP (NCI)Hs.244580
Alternative Splicing GalleryENSG00000088325
Gene ExpressionTPX2 [ NCBI-GEO ]   TPX2 [ EBI - ARRAY_EXPRESS ]   TPX2 [ SEEK ]   TPX2 [ MEM ]
Gene Expression Viewer (FireBrowse)TPX2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)22974
GTEX Portal (Tissue expression)TPX2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9ULW0   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9ULW0  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9ULW0
Splice isoforms : SwissVarQ9ULW0
PhosPhoSitePlusQ9ULW0
Domains : Interpro (EBI)Aurora-A-bd    TPX2_C    TPX2_central_dom    TPX2_fam   
Domain families : Pfam (Sanger)Aurora-A_bind (PF09041)    TPX2 (PF06886)    TPX2_importin (PF12214)   
Domain families : Pfam (NCBI)pfam09041    pfam06886    pfam12214   
Conserved Domain (NCBI)TPX2
DMDM Disease mutations22974
Blocks (Seattle)TPX2
PDB (SRS)1OL5    3E5A    3HA6    4C3P    5LXM   
PDB (PDBSum)1OL5    3E5A    3HA6    4C3P    5LXM   
PDB (IMB)1OL5    3E5A    3HA6    4C3P    5LXM   
PDB (RSDB)1OL5    3E5A    3HA6    4C3P    5LXM   
Structural Biology KnowledgeBase1OL5    3E5A    3HA6    4C3P    5LXM   
SCOP (Structural Classification of Proteins)1OL5    3E5A    3HA6    4C3P    5LXM   
CATH (Classification of proteins structures)1OL5    3E5A    3HA6    4C3P    5LXM   
SuperfamilyQ9ULW0
Human Protein AtlasENSG00000088325
Peptide AtlasQ9ULW0
HPRD05802
IPIIPI00008477   IPI00978939   IPI00102661   
Protein Interaction databases
DIP (DOE-UCLA)Q9ULW0
IntAct (EBI)Q9ULW0
FunCoupENSG00000088325
BioGRIDTPX2
STRING (EMBL)TPX2
ZODIACTPX2
Ontologies - Pathways
QuickGOQ9ULW0
Ontology : AmiGOG2/M transition of mitotic cell cycle  mitotic cell cycle  spindle pole  protein binding  ATP binding  GTP binding  nucleus  nucleoplasm  nucleoplasm  spindle  cytosol  microtubule  apoptotic process  cell proliferation  microtubule cytoskeleton  protein kinase binding  activation of protein kinase activity  axon hillock  cell division  regulation of mitotic spindle organization  importin-alpha family protein binding  mitotic spindle  mitotic spindle assembly  regulation of signal transduction by p53 class mediator  
Ontology : EGO-EBIG2/M transition of mitotic cell cycle  mitotic cell cycle  spindle pole  protein binding  ATP binding  GTP binding  nucleus  nucleoplasm  nucleoplasm  spindle  cytosol  microtubule  apoptotic process  cell proliferation  microtubule cytoskeleton  protein kinase binding  activation of protein kinase activity  axon hillock  cell division  regulation of mitotic spindle organization  importin-alpha family protein binding  mitotic spindle  mitotic spindle assembly  regulation of signal transduction by p53 class mediator  
Pathways : BIOCARTARole of Ran in mitotic spindle regulation [Genes]   
REACTOMEQ9ULW0 [protein]
REACTOME PathwaysR-HSA-8854518 [pathway]   
NDEx NetworkTPX2
Atlas of Cancer Signalling NetworkTPX2
Wikipedia pathwaysTPX2
Orthology - Evolution
OrthoDB22974
GeneTree (enSembl)ENSG00000088325
Phylogenetic Trees/Animal Genes : TreeFamTPX2
HOVERGENQ9ULW0
HOGENOMQ9ULW0
Homologs : HomoloGeneTPX2
Homology/Alignments : Family Browser (UCSC)TPX2
Gene fusions - Rearrangements
Fusion : MitelmanTM9SF4/TPX2 [20q11.21/20q11.21]  [t(20;20)(q11;q11)]  
Fusion : MitelmanTPX2/DEFB123 [20q11.21/20q11.21]  [t(20;20)(q11;q11)]  
Fusion : MitelmanTPX2/DUSP15 [20q11.21/20q11.21]  [t(20;20)(q11;q11)]  
Fusion : MitelmanTPX2/EYS [20q11.21/6q12]  [t(6;20)(q12;q11)]  
Fusion : MitelmanTPX2/HM13 [20q11.21/20q11.21]  [t(20;20)(q11;q11)]  
Fusion : MitelmanTPX2/RALY [20q11.21/20q11.22]  [t(20;20)(q11;q11)]  
Fusion : MitelmanTPX2/REM1 [20q11.21/20q11.21]  [t(20;20)(q11;q11)]  
Fusion : MitelmanTPX2/UNC5D [20q11.21/8p12]  [t(8;20)(p12;q11)]  
Fusion: TCGATM9SF4 20q11.21 TPX2 20q11.21 BRCA
Fusion: TCGATPX2 20q11.21 DEFB123 20q11.21 BRCA
Fusion: TCGATPX2 20q11.21 DUSP15 20q11.21 HNSC
Fusion: TCGATPX2 20q11.21 EYS 6q12 LUSC
Fusion: TCGATPX2 20q11.21 HM13 20q11.21 BLCA
Fusion: TCGATPX2 20q11.21 RALY 20q11.22 HNSC
Fusion: TCGATPX2 20q11.21 REM1 20q11.21 BLCA
Fusion: TCGATPX2 20q11.21 UNC5D 8p12 HNSC
Fusion Cancer (Beijing)TPX2 [20q11.21]  -  BCL2L1 [20q11.21]  [FUSC000210]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTPX2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TPX2
dbVarTPX2
ClinVarTPX2
1000_GenomesTPX2 
Exome Variant ServerTPX2
ExAC (Exome Aggregation Consortium)TPX2 (select the gene name)
Genetic variants : HAPMAP22974
Genomic Variants (DGV)TPX2 [DGVbeta]
DECIPHERTPX2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTPX2 
Mutations
ICGC Data PortalTPX2 
TCGA Data PortalTPX2 
Broad Tumor PortalTPX2
OASIS PortalTPX2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTPX2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTPX2
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 TPX2
DgiDB (Drug Gene Interaction Database)TPX2
DoCM (Curated mutations)TPX2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TPX2 (select a term)
intoGenTPX2
NCG5 (London)TPX2
Cancer3DTPX2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM605917   
Orphanet
MedgenTPX2
Genetic Testing Registry TPX2
NextProtQ9ULW0 [Medical]
TSGene22974
GENETestsTPX2
Target ValidationTPX2
Huge Navigator TPX2 [HugePedia]
snp3D : Map Gene to Disease22974
BioCentury BCIQTPX2
ClinGenTPX2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD22974
Chemical/Pharm GKB GenePA25638
Clinical trialTPX2
Miscellaneous
canSAR (ICR)TPX2 (select the gene name)
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=TPX2
Probes
Litterature
PubMed95 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTPX2
EVEXTPX2
GoPubMedTPX2
iHOPTPX2
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 : Fri Jun 30 11:20:30 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.