DDB1 and CUL4 associated factor 15 (DCAF15)

DDB1 and CUL4 associated factor 15 (DCAF15) is a substrate receptor protein component of the DCX(DCAF15) cullin-4-RING E3 ubiquitin-protein ligase complex, which determines substrate specificity by recruiting particular proteins for ubiquitination and subsequent proteasomal degradation. DCAF15 regulates immune functions such as natural killer (NK) cell effector activity and activation of antigen-presenting cells. Aryl sulfonamide drugs (e.g., indisulam, E7820) act as molecular glues that alter the substrate specificity of the DCAF15 complex, promoting degradation of splicing factors (notably RBM39), leading to cell death in some cancer cell types. DCAF15 is thus relevant as both a biological modulator and as a direct target of small molecule cancer therapeutics, with ongoing investigation into its wider physiological and disease roles

Other names

DCAF15C19orf72DDB1 and CUL4 associated factor 15

These drugs act as "molecular glues," changing DCAF15 substrate specificity so that the DCX(DCAF15) ubiquitin ligase polyubiquitinates the splicing factor RBM39 (and to a lesser extent RBM23 and PRPF39), leading to their proteasome-mediated degradation and resulting in splicing defects and subsequent cell death in cancer cells