Atlas of Genetics and Cytogenetics in Oncology and Haematology
UBE2C (ubiquitin-conjugating enzyme E2C)
| Identity |
| Other names | UBCH10 |
| UBE2C-PEN | |
| UbcH10 | |
| dJ447F3.2 | |
| LOC11065 | |
| HGNC | UBE2C |
| Location | 20q13.12 |
| Location_base_pair | Starts at 43874662 and ends at 43879003 bp from pter ( according to hg18-Mar_2006). |
| Local_order | CENTROMERE---WFDC3-DNTTIP1-UBE2C-TNNC2-SNX21-ACOT8---TELOMERE |
| Note | UbcH10 catalyzes the covalent attachment of ubiquitin to target proteins. It is required for the destruction of mitotic cyclins. |
| DNA/RNA |
| Description | UBE2C is located on chromosome 20, at 20q13.12 according to Entrez Gene. In AceView, it covers 4.40 kb, from 43874623 to 43879017 on the direct strand. |
| Transcription | There are 6 representative transcripts annotated in RefSeq database, but, according to AceView, Homo sapiens cDNA sequences in GenBank support at least 13 spliced variants. Isoform 1, the longest isoform, is composed of 6 coding exons of varying lengths, separated by introns: NM_007019.2 (mRNA-ubiquitin-conjugating enzyme E2C): mRNA product length: 823. |
| Protein |
| Description | The UbcH10 gene encodes a member of the E2 ubiquitin-conjugating enzyme family that is involved in the ubiquitin dependent proteolysis. In this pathway, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), together with ubiquitin ligase (E3), catalyze the covalent attachment of ubiquitin to target proteins, targeting them for degradation mediated by the 26S proteasome. The full-length UbcH10 contains 179 residues for a 19.6 kDa weight. It belongs to the class III Ubc proteins that are characterized by an NH2-terminal extension followed by the "core" Ubc fold. Like all E2 enzymes, UbcH10 contains an active site cysteine residue (position 114) that is crucial for the formation of the ubiquitin-thiolester. Alteration of this residue C(114)S strongly inhibits ubiquitination of cyclin A and Cyclin B confering a dominant-negative phenotype. Levels of UbcH10 are modulated by autoubiquitination. This process is dependent on a motif, the "destruction box" [Arg-X-X-Leu-X-X-(Leu/Ile)-X-Asp] recognized by the mitotic-specific ubiquitination machinery. A study suggests that a destruction box is present in the UbcH10 sequence and includes residues 129-132 (Arg-Thr-Ile-Leu). Interestingly an SNP is reported for the residue 129 (refSNP ID: rs7352110, alleles A/G, Arg>Gly). This would be important since any change in the putative destruction box could stabilize UbcH10 against destruction. |
| Expression | UbcH10 mRNA and protein are expressed at low levels in most adult normal tissues. In contrast, UbcH10 mRNA and protein are highly expressed in tumor tissues. Moreover, UbcH10 protein levels fluctuate during the cell cycle being abundant during M and early G1 phases, but decreasing in late G1, S and G2 phases. |
| Localisation | Nucleoplasm. Cytosol. |
| Function | UbcH10 is crucial for cell cycle progression during the G2/M phase, since its function is required for the destruction of mitotic cyclins and other mitosis-related substrates. UbcH10 interacts with the multiprotein complex APC (anaphase-promoting complex), which has E3 ubiquitin ligase activity, and targets for destruction substrates from the preceding mitosis (cyclin A, cyclin B, securin, geminin). Once these target proteins have been degraded, UbcH10 adds ubiquitins to itself, triggering its own destruction. As a result, the absence of UbcH10 allows the accumulation of cyclin A, which in turn contributes to the APC inactivation, providing a molecular switch that allows cells to proceed from cell division to a new round of DNA duplication. Hence, the function of UbcH10 is strictly linked to the progression of cell cycle through the M phase and the coupling of mitosis to S-phase entry via autonomous regulation of the anaphase-promoting complex. |
 | |
| Implicated in |
| Entity | Human cancers |
| Note | Several studies suggest a possible use of UbcH10 investigation (together with other molecular markers) in early detection of cancer. Other studies suggest that inhibition of UbcH10 could have a therapeutic potential in cancer treatment. |
| Disease | UbcH10 overexpression was reported in a number of human cancer cell lines and primary tumors and expression data strongly support an association between high UbcH10 expression and a poor tumor differentiation. Expression studies have also shown a correlation between UbcH10 overexpression and the proliferation status since there is a good association with the proliferation marker Ki-67/MIB1. It was found overexpressed in lung carcinoma ( squamous and adenocarcinoma, poorly versus well differentiated), bladder carcinoma (grade 3 versus grade 2), prostate carcinoma(metastatic versus primary), gastric adenocarcinoma cervical, esophageal adenocarcinoma(adenocarcinoma versus Barrett's metaplasia), breast cancer (grade 3 versus grade 1, malignant versus benign neoplastic lesions), brain ( astrocytomas versus low-grade tumors or normal controls), medulloblastoma, ovarian carcinoma (grade 3 versus grade 1 and 2), thyroid carcinoma (poorly versus well differentiated), adrenocortical gland, Wilms tumor (relapsed versus relapse-free) hepatocellular carcinoma (correlation with higher frequencies of invasion to capsular formation, invasion to portal vein and tumor de-differentiation). Several expression analysis and functional studies have also shown that UbcH10 resulted up-regulated in experimental model of carcinogenesis, that its overexpression lead to the acquisition of a malignant phenotype and that its knockdown successfully resulted in growth arrest. |
| Prognosis | It was seen that UbcH10 overexpression is a negative predictor of clinical outcome in patients affected by ovarian and hepatocellular carcinoma. Therefore, UbcH10 has been suggested as an helpful prognostic indicator for ovarian and hepatocellular carcinoma patients. |
| Oncogenesis | 20q13.1 chromosomal region is frequently associated with genomic amplification in different malignant neoplasias and amplification of UbcH10 locus has been reported in the case of gastroesophageal carcinomas, colorectal carcinomas with liver metastases, cervical cancers, ovarian carcinomas, gliomas and culture cell lines obtained from anaplastic thyroid carcinomas. |
| External links |
| Bibliography |
| Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation. |
| Yu H, King RW, Peters JM, Kirschner MW. |
| Curr Biol 1996; 6: 455-66. |
| PMID 8723350 |
| Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase. |
| Townsley FM, Aristarkhov A, Beck S, Hershko A, Ruderman JV. |
| Proc Natl Acad Sci U S A 1997; 94: 2362-7. |
| PMID 9122200 |
| APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. |
| Tang Z, Li B, Bharadwaj R, Zhu H, Ozkan E, Hakala K, Deisenhofer J, Yu H. |
| Mol Biol Cell 2001; 12: 3839-51. |
| PMID 11739784 |
| Molecular characterization of plant ubiquitin-conjugating enzymes belonging to the UbcP4/E2-C/UBCx/UbcH10 gene family. |
| Criqui MC, de Almeida Engler J, Camasses A, Capron A, Parmentier Y, Inze D, Genschik P. |
| Plant Physiol 2002; 130: 1230-40. |
| PMID 12427990 |
| Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10. |
| Lin Y, Hwang WC, Basavappa R. |
| J Biol Chem 2002; 277: 21913-21. |
| PMID 11927573 |
| UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme. |
| Okamoto Y, Ozaki T, Miyazaki K, Aoyama M, Miyazaki M, Nakagawara A. |
| Cancer Res 2003; 63: 4167-73. |
| PMID 12874022 |
| A molecular 'signature' of primary breast cancer cultures; patterns resembling tumor tissue. |
| Dairkee SH, Ji Y, Ben Y, Moore DH, Meng Z, Jeffrey SS. |
| BMC Genomics 2004; 5:47. |
| PMID 15260889 |
| Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry. |
| Rape M, Kirschner MW. |
| Nature 2004; 432: 588-95. |
| PMID 15558010 |
| Overexpression, genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin. |
| Wagner KW, Sapinoso LM, El-Rifai W, Frierson HF, Butz N, Mestan J, Hofmann F, Deveraux QL, Hampton GM. |
| Oncogene 2004; 23: 6621-9. |
| PMID 15208666 |
| Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas. |
| Bredel M, Bredel C, Juric D, Harsh GR, Vogel H, Recht LD, Sikic BI. |
| Cancer Res 2005; 65: 8679-89. |
| PMID 16204036 |
| In silico chromosomal clustering of genes displaying altered expression patterns in ovarian cancer. |
| Israeli O, Goldring-Aviram A, Rienstein S, Ben-Baruch G, Korach J, Goldman B, Friedman E. |
| Cancer Genet Cytogenet 2005; 160: 35-42. |
| PMID 15949568 |
| A novel UbcH10-binding protein facilitates the ubiquitinylation of cyclin B in vitro. |
| Kobirumaki F, Miyauchi Y, Fukami K, Tanaka H. |
| J Biochem 2005; 137: 133-9. |
| PMID 15749827 |
| UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas. |
| Pallante P, Berlingieri MT, Troncone G, Kruhoffer M, Orntoft TF, Viglietto G, Caleo A, Migliaccio I, Decaussin-Petrucci M, Santoro M, Palombini L, Fusco A. |
| Br J Cancer 2005; 93: 464-71. |
| PMID 16106252 |
| Combination of multiple mRNA markers (PTTG1, Survivin, UbcH10 and TK1) in the diagnosis of Taiwanese patients with breast cancer by membrane array. |
| Chen CC, Chang TW, Chen FM, Hou MF, Hung SY, Chong IW, Lee SC, Zhou TH, Lin SR. |
| Oncology 2006; 70: 438-46. |
| PMID 17220641 |
| Before and after the spindle assembly checkpoint--an APC/C point of view. |
| de Gramont A, Ganier O, Cohen-Fix O. |
| Cell Cycle 2006; 5: 2168-71. |
| PMID 16969093 |
| Expression and effect of inhibition of the ubiquitin-conjugating enzyme E2C on esophageal adenocarcinoma. |
| Lin J, Raoof DA, Wang Z, Lin MY, Thomas DG, Greenson JK, Giordano TJ, Orringer MB, Chang AC, Beer DG, Lin L. |
| Neoplasia 2006; 8: 1062-71. |
| PMID 17217624 |
| The anaphase promoting complex/cyclosome: a machine designed to destroy. |
| Peters JM. |
| Nat Rev Mol Cell Biol 2006; 7: 644-56. Review. |
| PMID 16896351 |
| The processivity of multiubiquitination by the APC determines the order of substrate degradation. |
| Rape M, Reddy SK, Kirschner MW. |
| Cell 2006; 124: 89-103. |
| PMID 16413484 |
| Detection of aberrations of ubiquitin-conjugating enzyme E2C gene (UBE2C) in advanced colon cancer with liver metastases by DNA microarray and two-color FISH. |
| Takahashi Y, Ishii Y, Nishida Y, Ikarashi M, Nagata T, Nakamura T, Yamamori S, Asai S. |
| Cancer Genet Cytogenet 2006; 168: 30-5. |
| PMID 16772118 |
| Expression profiling of Wilms tumors reveals new candidate genes for different clinical parameters. |
| Zirn B, Hartmann O, Samans B, Krause M, Wittmann S, Mertens F, Graf N, Eilers M, Gessler M. |
| Int J Cancer 2006; 118: 1954-62. |
| PMID 16287080 |
| UbcH10 expression may be a useful tool in the prognosis of ovarian carcinomas. |
| Berlingieri MT, Pallante P, Guida M, Nappi C, Masciullo V, Scambia G, Ferraro A, Leone V, Sboner A, Barbareschi M, Ferro A, Troncone G, Fusco A. |
| Oncogene 2007; 26: 2136-40. |
| PMID 17016443 |
| UbcH10 is overexpressed in malignant breast carcinomas. |
| Berlingieri MT, Pallante P, Sboner A, Barbareschi M, Bianco M, Ferraro A, Mansueto G, Borbone E, Guerriero E, Troncone G, Fusco A. |
| Eur J Cancer 2007; 43: 2729-35. |
| PMID 17933517 |
| Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression. |
| Ieta K, Ojima E, Tanaka F, Nakamura Y, Haraguchi N, Mimori K, Inoue H, Kuwano H, Mori M. |
| Int J Cancer 2007; 121: 33-8. |
| PMID 17354233 |
| Molecular cytogenetic profiles of novel and established human anaplastic thyroid carcinoma models. |
| Lee JJ, Foukakis T, Hashemi J, Grimelius L, Heldin NE, Wallin G, Rudduck C, Lui WO, Hoog A, Larsson C. |
| Thyroid 2007; 17: 289-301. |
| PMID 17465858 |
| Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes. |
| Narayan G, Bourdon V, Chaganti S, Arias-Pulido H, Nandula SV, Rao PH, Gissmann L, Durst M, Schneider A, Pothuri B, Mansukhani M, Basso K, Chaganti RS, Murty VV. |
| Genes Chromosomes Cancer 2007; 46: 373-84. |
| PMID 17243165 |
| Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation. |
| Reddy SK, Rape M, Margansky WA, Kirschner MW. |
| Nature 2007; 446: 921-5. |
| PMID 17443186 |
| Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. |
| Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, McDonald ER 3rd, Li MZ, Hannon GJ, Sorger PK, Kirschner MW, Harper JW, Elledge SJ. |
| Nature 2007; 446: 876-81. |
| PMID 17443180 |
| Estrogen-regulated gene expression predicts response to endocrine therapy in patients with ovarian cancer. |
| Walker G, MacLeod K, Williams AR, Cameron DA, Smyth JF, Langdon SP. |
| Gynecol Oncol. 2007 Sep;106(3):461-8. |
| PMID 17624412 |
| Prediction of metastatic relapse in node-positive breast cancer: establishment of a clinicogenomic model after FEC100 adjuvant regimen. |
| Campone M, Campion L, Roche H, Gouraud W, Charbonnel C, Magrangeas F, Minvielle S, Geneve J, Martin AL, Bataille R, Jezequel P. |
| Breast Cancer Res Treat 2008; 109: 491-501. |
| PMID 17659439 |
| Expression of ubiquitin-conjugating enzyme E2C/UbcH10 in astrocytic tumors. |
| Jiang L, Huang CG, Lu YC, Luo C, Hu GH, Liu HM, Chen JX, Han HX. |
| Brain Res 2008; 1201: 161-6. |
| PMID 18331723 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 06-2008 | Pierlorenzo Pallante, Maria Teresa Berlingieri, Alfredo Fusco |
| Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facolta di Medicina e Chirurgia, Universita degli Studi di Napoli "Federico II", via Pansini 5, 80131 Napoli, Italy |
| Citation |
| This paper should be referenced as such : |
| Pallate P, Berlingieri MT, Fusco A . UBE2C (ubiquitin-conjugating enzyme E2C). Atlas Genet Cytogenet Oncol Haematol. June 2008 . URL : http://AtlasGeneticsOncology.org/Genes/UBE2CID44079ch20q13.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sun Nov 9 19:49:22 2008 |
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