DDB1- and CUL4-associated factor 5 (DCAF5)

DDB1- and CUL4-associated factor 5 (DCAF5) is a substrate receptor protein for the CUL4-DDB1 E3 ubiquitin ligase complex[2][6]. It contains WD repeat domains and mediates ubiquitination and degradation of specific protein substrates, including incompletely assembled SWI/SNF chromatin remodeling complexes in the absence of SMARCB1[1][4][2]. DCAF5 is essential for the survival of SMARCB1-mutant cancer cells because it clears defective SWI/SNF complexes, a process critical to the oncogenic state in these cancers. Loss or inhibition of DCAF5 in SMARCB1-deficient cells leads to reaccumulation of functional chromatin remodeling complexes and reversal of malignancy phenotypes[1][4]. DCAF5 also plays roles in developmental regulation and cellular homeostasis, with genomic deletion associated with neurodevelopmental phenotypes[2][5][7]. Its WD repeat domain structure provides a potential druggable site, but clinical inhibitors or drugs directly targeting DCAF5 are not yet established[4].

Other names

BCRG2KIAA1824WDR22BCRP2D14S1461EBreakpoint cluster region protein 2WD repeat-containing protein 22

Targeting DCAF5 inhibits its E3 ligase function, stabilizes partially assembled SWI/SNF complexes, and restores chromatin remodeling activity in SMARCB1-mutant cancers[1][4].