Cullin-4B (CUL4B)

Cullin‐4B is an evolutionarily conserved scaffold protein that forms the core component of the cullin-RING E3 ubiquitin ligase complex known as CRL4^CUL-B. This complex mediates polyubiquitination and subsequent proteasomal degradation or functional modification of numerous substrate proteins involved in cell cycle control, chromatin remodeling, DNA repair, neural development, adipogenesis, tumorigenesis/progression, immune response modulation, and epigenetic gene silencing through histone monoubiquitination. Mutations or dysregulation can lead to neurodevelopmental disorders such as X-linked intellectual disability syndromes and contribute to oncogenesis by altering cell proliferation pathways. While not directly targeted by current therapeutics except indirectly via Cereblon-binding agents like thalidomide derivatives used primarily for their immunomodulatory/anti-cancer properties, its central role makes it an area of active research interest for drug discovery efforts focused on modulating protein homeostasis machinery.

Other names

CUL-4bCullin 4bX-linked mental retardation gene MRXHF1

For drugs like thalidomide:\n - Modulation/degradation of substrate proteins through recruitment to CRL complexes containing Cereblon.\n - Indirect effects on transcriptional repression via epigenetic modifications mediated by CRL activity.\nNo direct small-molecule inhibitors or activators are currently established for clinical use.