- UBE2C (Ubiquitin-conjugating enzyme E2 C) is a specialized member of the E2 ubiquitin-conjugating enzyme family that plays a pivotal role in regulating the cell cycle, particularly during the transition from metaphase to anaphase. It is also known as UbcH10.
- Like other E2 enzymes, UBE2C works in concert with ubiquitin-activating (E1) and ubiquitin-ligating (E3) enzymes to attach ubiquitin to target proteins, marking them for degradation or functional modification. What distinguishes UBE2C is its partnership with the anaphase-promoting complex/cyclosome (APC/C), a large multi-subunit E3 ubiquitin ligase that controls mitotic progression by regulating the timely destruction of key cell cycle proteins.
- UBE2C is essential for initiating APC/C-dependent polyubiquitination of mitotic regulators such as cyclin B, securin, and other substrates that must be degraded for sister chromatid separation and exit from mitosis. By working with APC/C, UBE2C helps assemble polyubiquitin chains, predominantly K11-linked, which serve as degradation signals for the proteasome. Its activity ensures that cells maintain proper genomic integrity, preventing premature or delayed progression through mitosis. UBE2C, along with UBE2S (another E2 with APC/C specificity), provides a complementary function—UBE2C initiates ubiquitin chain formation, while UBE2S extends the chains to enhance degradation efficiency.
- Dysregulation of UBE2C is strongly associated with cancer biology. UBE2C is frequently overexpressed in a wide range of human malignancies, including breast, lung, prostate, colorectal, and ovarian cancers. Elevated UBE2C levels correlate with increased cell proliferation, chromosomal instability, and poor prognosis. Overactive UBE2C can override normal cell cycle checkpoints, driving uncontrolled mitotic progression and contributing to tumorigenesis. As such, UBE2C is considered both a biomarker of cancer progression and a potential therapeutic target. Inhibiting UBE2C function may restore normal cell cycle regulation and reduce tumor growth, making it an attractive focus of anticancer drug development.
- Beyond oncology, UBE2C dysfunction has implications in genomic instability disorders. Experimental depletion of UBE2C results in prolonged mitosis, activation of spindle checkpoint pathways, and defects in chromosome segregation. Conversely, its overexpression drives premature degradation of mitotic regulators and aneuploidy. Thus, maintaining balanced UBE2C activity is critical for cellular homeostasis.
- Structurally, UBE2C contains the conserved ubiquitin-conjugating (UBC) catalytic domain, with its active-site cysteine forming a thioester intermediate with ubiquitin. Unlike some other E2 families, UBE2C has sequence features that optimize its specific interaction with the APC/C complex. This structural specialization explains its relatively narrow but essential role in cell cycle regulation compared to more promiscuous E2 enzymes like UBE2D.
- In summary, UBE2C is a cell cycle–specific E2 enzyme that partners with APC/C to regulate the ubiquitination and degradation of mitotic regulators. Its function is essential for accurate mitotic progression and genomic stability. Dysregulation, particularly overexpression, is tightly linked to tumor development and progression, making UBE2C both a crucial regulator of mitosis and an important biomarker and therapeutic target in cancer.
Reliability Index *****
Note: If you notice any errors or inconsistencies, we welcome your feedback. Please share your observations in the comment box below — your input helps us improve.
Highest reliability: *****
Lowest reliability: *****
