E3 ubiquitin-protein ligase BRE1B (RNF40)

E3 ubiquitin-protein ligase BRE1B (RNF40) is an enzyme encoded by the RNF40 gene in humans and forms a stable heterodimeric complex with RNF20, known as the RNF20/40 complex[1][2][4]. This complex catalyzes the monoubiquitylation of histone H2B at lysine 120, a critical epigenetic modification involved in the regulation of gene transcription, chromatin remodeling, and genome stability[1][4]. RNF40 is ubiquitously expressed and contains characteristic coiled-coil domains and a C-terminal RING finger motif, which facilitate protein–protein and protein–DNA interactions[1][3]. Through its activity, RNF40 influences DNA damage repair, apoptosis, and cell cycle progression, playing essential roles in tumor suppression and, paradoxically, in oncogenesis depending on cellular context[1][2][5]. The RNF20/40 complex modulates gene expression in response to cellular stress, including DNA damage, and interacts with key regulators such as the tumor suppressor p53[2]. Alterations in RNF40 function or expression have been implicated in various cancers, making it a potential, but as yet not clinically validated, therapeutic target and biomarker[1][2][5].

Other names

BRE1BKIAA0661RBP95STARING95 kDa retinoblastoma-associated proteinRING finger protein 40RING-type E3 ubiquitin transferase BRE1BBRE1 E3 ubiquitin ligase homolog BRb-associated proteinE3 ubiquitin protein ligase

Not directly targeted by approved drugs; potential mechanism would be inhibition or modulation of E3 ubiquitin ligase activity affecting H2B ubiquitylation and downstream transcriptional regulation