UBE2C

UBE2C Full Name

ubiquitin-conjugating enzyme E2C

UBE2C Introduction

Ubiquitin-conjugating enzyme E2C (UBE2C), also known as UbcH10, is a member of the ubiquitin-conjugating enzyme (E2) family that plays a central and specialized role in the regulation of mitotic progression. Encoded by the UBE2C gene on chromosome 20q13.12, UBE2C functions as the cognate E2 enzyme for the anaphase-promoting complex/cyclosome (APC/C), a large multisubunit E3 ubiquitin ligase that governs the metaphase-to-anaphase transition and mitotic exit. UBE2C is distinguished from most other E2 enzymes by its highly restricted expression and activity profile: its levels are virtually undetectable in G0/G1, rise during S and G2 phases, peak at mitosis, and are rapidly degraded following APC/C-mediated ubiquitination as cells exit mitosis.

Figure 1. Strcuture of UBE2C.

APC/C-Mediated Ubiquitination and Cell Cycle Control
UBE2C catalyzes the transfer of ubiquitin from its active site cysteine to lysine residues on APC/C substrates, with a critical role in the formation of polyubiquitin chains that target substrates for proteasomal degradation. During mitosis, UBE2C-APC/C complexes ubiquitinate two key substrates: securin (an inhibitor of the separase protease) and cyclin B1 (the regulatory subunit of cyclin-dependent kinase 1/CDK1). Degradation of securin releases active separase, which cleaves the cohesin rings holding sister chromatids together, permitting chromosome segregation at anaphase onset. Concurrent degradation of cyclin B1 inactivates CDK1, driving mitotic exit. UBE2C possesses a unique C-terminal extension, not present in other E2 enzymes, that mediates processive polyubiquitin chain assembly directly on APC/C substrates — this property makes UBE2C an exceptionally efficient E2 for processive ubiquitination and distinguishes it from the other APC/C cognate E2, UBE2S, which extends pre-initiated ubiquitin chains.

UBE2C Overexpression in Cancer: A Driver of Chromosomal Instability
UBE2C is one of the most consistently overexpressed genes across human cancers, with elevated transcript and protein levels reported in carcinomas of the breast, lung, colon, ovary, liver, bladder, and prostate, as well as in glioblastoma and multiple hematological malignancies. UBE2C overexpression is not merely a passive consequence of increased proliferation but actively contributes to oncogenesis: supraphysiological UBE2C levels accelerate the degradation of APC/C substrates, potentially overriding the spindle assembly checkpoint, leading to premature anaphase onset and chromosomal missegregation — a major driver of chromosomal instability (CIN). High UBE2C expression correlates with advanced tumor grade, lymph node metastasis, and poor overall survival across multiple cancer types and has been validated as an independent prognostic marker. UBE2C is also implicated in resistance to microtubule-targeting chemotherapeutic agents (e.g., paclitaxel, vincristine), as cells with elevated UBE2C can more readily bypass the mitotic arrest induced by these drugs. Selective small-molecule inhibitors of UBE2C are under active investigation as a strategy to target CIN-positive cancers and overcome taxane resistance in breast and ovarian cancer.

Alternate Names for UBE2C

UBE2C; ubiquitin-conjugating enzyme E2C; ubiquitin-conjugating enzyme E2 C; UBCH10; ubiquitin-protein ligase C; ubiquitin carrier protein C; ubiquitin carrier protein E2-C; cyclin-selective ubiquitin carrier protein; mitotic-specific ubiquitin-conjugating enzyme; dJ447F3.2;