Cullin-5 (CUL5)

Cullin-5 (CUL5) is a core component of the cullin-RING E3 ubiquitin ligase (CRL5) complex, acting as a scaffold to assemble multiple subunits involved in substrate recognition and targeted protein degradation by the ubiquitin-proteasome pathway[1][2][4]. CUL5 mediates the ubiquitination and proteasomal degradation of diverse cellular proteins, thus regulating key biological processes including cell proliferation, migration, DNA damage response, angiogenesis, and autophagy[4]. In disease, CUL5 expression is commonly downregulated in cancers, correlating with altered cell growth and signaling. It is hijacked by viral proteins such as HIV-1 Vif to degrade host restriction factors, supporting viral replication[2]. CUL5 is a subject of research interest as a potential anticancer and antiviral therapeutic target, though no direct modulators are clinically approved[3][4].

Other names

Cullin-5CUL5VACM1VACM-1Vasopressin-activated calcium-mobilizing receptor 1

Drugs targeting CUL5 would be expected to alter ubiquitin-mediated proteasomal degradation of substrates. For viral infection, hijacking of CUL5 by HIV-1 Vif enables degradation of APOBEC3 proteins[2].