Cullin 4A (CUL4A)

Cullin 4A (CUL4A) is an 87-kDa scaffold protein that serves as a central organizer of the CRL4 E3 ubiquitin ligase complex[1][2]. It interacts with core subunits (ROC1/Rbx1) and the substrate adaptor DDB1, which in turn recruits diverse substrate receptors (DCAFs) to mediate ubiquitination of many major regulators. CUL4A complexes mediate critical processes such as cell cycle progression, DNA repair, chromatin remodeling, and maintenance of genomic stability. Dysfunction or overexpression of CUL4A is linked to oncogenesis, making CUL4A a promising drug target; its pathway is also exploited by certain viruses to promote their survival. CUL4A's prognostic and predictive utility in cancer, and its role in key cell processes, has led to interest in developing targeted inhibitors, though most current drugs modulate related adaptors rather than CUL4A directly[1][2][3].

Other names

CUL4ACullin-4ACullin family protein 4A

Drugs such as lenalidomide and other immunomodulatory agents redirect CRL4 complex substrate specificity by binding to the CRL4^CRBN^ complex (an adaptor complex using CUL4A as the scaffold)[2] Direct inhibition of the E3 ligase activity would require blocking substrate recruitment and/or catalytic activity[1]