Cereblon (CRBN)

Cereblon (CRBN) is a protein encoded by the CRBN gene and functions as the substrate receptor component of the CRL4^CRBN^ E3 ubiquitin ligase complex[2][5]. It regulates protein ubiquitination and degradation, thus influencing diverse processes such as cell proliferation, apoptosis, metabolic regulation, and developmental pathways[1][3]. As the direct protein target for thalidomide and its analogs (IMiDs, or Cereblon E3 ligase modulators), CRBN is essential for their therapeutic and toxic effects, including anti-myeloma activity and teratogenicity[4][6]. CRBN also has cytoplasmic chaperone activities that affect the folding and maturation of various transmembrane proteins[3]. Disruption or pharmacological modulation of CRBN alters downstream signaling (including immune and angiogenic pathways), making it a critical therapeutic target in treating multiple myeloma and other malignancies[4][6].

Other names

Cereblon E3 ubiquitin ligaseCRBN E3 ligaseCereblon protein

- Redirects substrate specificity of the CRL4^CRBN^ E3 ubiquitin ligase complex to promote degradation of neosubstrates, leading to antiproliferative and immunomodulatory effects - Inhibits pro-inflammatory cytokine production (including TNF-α and IL-6) - Co-stimulates T cell and NK cell activation - Inhibits angiogenesis by decreasing VEGF - Alters maturation and trafficking of membrane proteins in a chaperone-dependent fashion[3][4][5][6]