N-terminal domain of DDB1- and CUL4-associated factor 15
This model represents the N-terminal domain of DCAF15 (DDB1- and CUL4-associated factor 15), the cullin RING ligase substrate receptor/adaptor that forms a complex with CUL4A or CUL4B, as part of the Rbx-Cul4-DDA1-DDB1-DCAF15 E3 ubiquitin ligase that is responsible for the proteasome degradation of certain proteins. Aryl sulfonamide anticancer agents such as indisulam, tasisulam, E7820, and chloroquinoxaline have been shown to recruit the essential mRNA-splicing factor RBM39 to DCAF15. These agents appear to promote binding of DCAF15 to the RNA-recognition motif (RRM) of RBM39, which suggests that derivatives of the aryl-sulfonamides may be used to target other RRM-containing proteins. Cell proliferation is inhibited by these aryl sulfonamides by causing degradation of RBM39, which leads to aberrant processing of pre-mRNA in hundreds of genes, primarily reflected by intron retention and exon skipping, thus collectively referred to as splicing inhibitor sulfonamides, or SPLAMs.