Ubiquitin-conjugating enzyme E2C: a potential cancer biomarker

Abstract

The ubiquitin-conjugating enzymes 2C (UBE2C) is an integral component of the ubiquitin proteasome system. UBE2C consists of a conserved core domain containing the catalytic Cys residue and an N-terminal extension. The core domain is required for ubiquitin adduct formation by interacting with the ubiquitin-fold domain in the E1 enzyme, and contributes to the E3 enzyme binding. UBE2C N-terminal extension regulates E3 enzyme activity as a part of an intrinsic inhibitory mechanism. UBE2C is required for the destruction of mitotic cyclins and securin, which are essential for spindle assembly checkpoint and mitotic exit. The UBE2C mRNA and/or protein levels are aberrantly increased in many cancer types with poor clinical outcomes. Accumulation of UBE2C stimulates cell proliferation and anchorage-independent growth. UBE2C transgenic mice are prone to develop spontaneous tumors and carcinogen-induced tumor with evidence of chromosome aneuploidy.

Keywords: 3(10); 3(10)-helix; APC/C; ATRA; Anaphase-promoting complex; B1-4; BUB receptor 1; BUB3; BubR1; CCI-779; CDC20; CDK; CP1A/C; Cancer; Cdh1; D-box; DUBs; E1; E2; E2F; E3; G(1); G(2); H1-4; JNK; Jun N-terminal kinases; KEN-box; M; MAD 2; MED1; Meis-1; N-terminal; NF-1; NIH3T3; Pax-2; QNP; RING; RWD; S; S-phase kinase-associated protein 2; SCF; SRF; Skp1-Cullin-Fox complex; Skp2; UBE2C; UPS; USP44; UbcH10; Ubiquitin-conjugating enzymes 2C; Ubiquitination; all-trans retinoic acid; amino acid-terminal; anaphase-promoting complex/cyclosome; avian myelocytomatosis virus oncogene cellular homolog; budding uninhibited by benzimidazoles 3; c-Myc; c-Rel; cadherin-1; calpain-1 A/C; cell cycle inhibitor-779; cell division cycle 20; cyclin-dependent kinase; destruction box; deubiquitination enzymes; domain, domain find in RING finger-WD repeat domain containing protein; elongation 2 transcription factor; finger domain, really interesting new gene finger domain; gap 1 phase; gap 2 phase; human ubiquitin-conjugating enzyme 10; mRNA; mediator-1; messenger ribonucleic acid; mitosis phase; mitotic arrest deficient-like 2; motif, Gln(4), Asn(5) and Pro(8) motif; myeloid ecotropic viral integration site 1; neurofibromin 1; paxillin 2; primary mouse embryonic fibroblast; reticuloendotheliosis oncogene cellular homolog; serum response factor; synthesis phase; the amino acid sequence KEN(X)(n)P; ubiquitin ligase; ubiquitin proteasome system; ubiquitin specific peptidase 44; ubiquitin-activating enzyme; ubiquitin-conjugating enzyme; ubiquitin-conjugating enzyme E2; α-helices; β-sheets.