Ubiquitin-conjugating enzyme E2 B (UBE2B) (UBE2B)

Ubiquitin-conjugating enzyme E2 B (UBE2B), also known as RAD6B, is a highly conserved enzyme that plays a pivotal role in the ubiquitin-proteasome system by catalyzing the covalent attachment of ubiquitin to target proteins (UniProt P63146). It is a key component of the DNA damage bypass pathway, where it interacts with the E3 ligase RAD18 to monoubiquitinate PCNA, enabling translesion synthesis and post-replication repair (PubMed: 17130289). UBE2B also mediates the monoubiquitination of histone H2B at Lys-120, a modification essential for transcriptional activation and chromatin remodeling (PubMed: 16337599). In clinical contexts, UBE2B is often overexpressed in various malignancies, including breast, ovarian, and colorectal cancers, where it contributes to tumor progression and resistance to DNA-damaging chemotherapies like carboplatin and carmustine (PubMed: 38481990, 29626515). Experimental inhibitors such as SMI#9 and TZ9 have been developed to target UBE2B/RAD6 activity, showing potential in sensitizing chemoresistant cancer cells (PubMed: 25303987). However, therapeutic targeting of UBE2B poses challenges, particularly regarding its essential role in spermatogenesis and the maintenance of genomic stability (PubMed: 11553617).

Other names

RAD6BHR6BHHR6BUBC2E2-17kDaUbiquitin carrier protein BUbiquitin-protein ligase B

Inhibition of ubiquitin-conjugating activity