DCAF15-DDB1 Protein, Human (sf9)

DCAF15 functions as the substrate-recognition component within the DCX(DCAF15) complex, a cullin-4-RING E3 ubiquitin-protein ligase complex responsible for ubiquitination and subsequent degradation of target proteins. This complex acts as a regulator of natural killer (NK) cell effector functions, potentially by targeting cohesin subunits SMC1A and SMC3 for ubiquitination and degradation. Additionally, DCAF15 may play a role in the activation of antigen-presenting cells (APC) and their interaction with NK cells. Notably, the substrate specificity of the DCX(DCAF15) complex is altered in the presence of aryl sulfonamide anticancer drugs, such as indisulam or E7820. This alteration promotes the ubiquitination and degradation of splicing factor RBM39, leading to splicing defects and cell death in cancer cell lines. These drugs act as molecular glues, facilitating the binding between DCAF15 and RBM39, and also induce ubiquitination and degradation of RBM23 and PRPF39. The unique properties of aryl sulfonamide anticancer drugs highlight DCAF15's pivotal role in modulating substrate specificity and cellular responses within the DCX(DCAF15) complex.