DDB1-and-CUL4-associated factor 1 (DCAF1)

DDB1-and-CUL4-associated factor 1 (DCAF1), also known as VprBP, is a critical substrate receptor for the Cullin 4-RING E3 ubiquitin ligase (CRL4) complex (UniProt Q9Y471). It serves as the primary intracellular machinery responsive to the HIV-1 Viral Protein R (Vpr), which hijacks the complex to trigger the ubiquitination and proteasomal degradation of various host cellular proteins (PubMed: 15105460). This interaction results in a characteristic G2/M phase cell cycle arrest and the eventual induction of apoptosis. In oncology, this pathway is exploited by targeting tumor cells that maintain the CRL4-DCAF1 complex, using Vpr or Vpr-mimetic agents to trigger cell death in a manner that often bypasses traditional p53-dependent pathways (PubMed: 16439195). Experimental approaches utilize Vpr-derived peptides or gene therapy vectors to deliver Vpr directly to tumor sites, leveraging the cell's own machinery to trigger mitotic catastrophe (PubMed: 22431512). Because many cancer cells possess defective G1/S checkpoints, they are particularly sensitive to the G2/M arrest and DNA damage response pathways modulated by the Vpr-DCAF1 interaction.

Other names

Vpr-binding proteinVprBPDDB1- and CUL4-associated factor 1RIP

Hijacking of the CRL4-DCAF1 E3 ubiquitin ligase complex to induce proteasomal degradation of specific host substrates, leading to G2/M phase cell cycle arrest and apoptosis.