Retinoblastoma-binding protein 6, ubiquitin ligase (RBBP6)

Retinoblastoma-binding protein 6, ubiquitin ligase (RBBP6) is a multi-domain E3 ubiquitin ligase characterized by a RING finger-like or U-box domain and an N-terminal ubiquitin-like domain. It functions in ubiquitination, facilitating degradation of substrates such as p53 and YBX1 through the proteasome, thereby modulating cell cycle progression, apoptosis, and cell proliferation. RBBP6 interacts directly with tumor suppressors (p53, Rb), influences mRNA processing via its association with the cleavage and polyadenylation machinery, and participates in protein quality control in concert with molecular chaperones such as Hsp70/Hsp40. RBBP6 is essential for the maintenance of glioblastoma stem cells via the ubiquitination and stabilization of CPSF3, impacting MYC expression and tumorigenesis. Dysregulation or overexpression is implicated in several cancers, and pharmacologic targeting of this pathway is an area of therapeutic interest, though its pleiotropic roles in cell biology present substantial therapeutic challenges.

Other names

E3 ubiquitin-protein ligase RBBP6RB Binding Protein 6P2P-RPACTSNAMAProliferation potential-related proteinRING-type E3 ubiquitin transferase RBBP6Retinoblastoma-binding Q protein 1p53-associated cellular protein of testisMy038RBQ-1Protein P2P-RRB-binding Q-protein 1

Drugs (like JTE-607) that inhibit CPSF3 can disrupt the RBBP6-mediated stabilization of CPSF3, affecting alternative polyadenylation and oncogene (MYC) regulation in glioblastoma