Ubiquitin-conjugating enzyme E2 F (UBE2F)

Ubiquitin-conjugating enzyme E2 F (UBE2F) is an E2-class enzyme that specializes in the conjugation of NEDD8, a ubiquitin-like molecule, to specific substrate proteins in a process known as neddylation. UBE2F is mechanistically distinct from its paralog UBE2M, as UBE2F selectively interacts with the E3 ligase RNF7 (also known as RBX2/SAG) to specifically neddylate cullin-5 (CUL5), but not other cullin family proteins. This neddylation facilitates the activation of the Cullin-RING ligase 5 (CRL5) complex, which promotes proteasomal degradation of target proteins via atypical K11-linked polyubiquitylation. In cancer, particularly non-small cell lung cancer, high UBE2F activity is correlated with increased degradation of the pro-apoptotic protein NOXA, thereby favoring tumor cell survival and poor patient prognosis. UBE2F inhibition has been shown to restore NOXA levels, induce apoptosis, and sensitize cancer cells to chemotherapeutic agents, highlighting its potential as a novel anti-cancer target. UBE2F also plays a role in viral infection models (e.g., HIV-1) by facilitating the degradation of antiviral proteins such as APOBEC3G through CUL5 neddylation.

Other names

NEDD8-conjugating enzyme UBE2FNCE2NEDD8 carrier protein UBE2FNEDD8 protein ligase UBE2FNEDD8-conjugating enzyme 2RING-type E3 NEDD8 transferase UBE2FUbiquitin-conjugating enzyme E2F (putative)NEDD8 conjugating enzyme

Inhibitors may block cullin-5 neddylation by binding to UBE2F, inactivating CRL5 and preventing degradation of pro-apoptotic proteins such as NOXA