DDB1 and CUL4 associated factor 15–RNA-binding motif protein 39 complex (DCAF15–RBM39 complex)

The DCAF15–RBM39 complex is formed when DCAF15, acting as an adaptor for the CRL4-DCAF15 E3 ubiquitin ligase, binds the splicing factor RBM39. Certain anticancer drugs, known as aryl sulfonamides (e.g., indisulam, E7820), function as molecular glues that promote this interaction, resulting in RBM39’s ubiquitination and subsequent proteasomal degradation. Because RBM39 is essential for pre-mRNA splicing and cell survival, its drug-induced removal can block cancer cell proliferation. This mechanism exemplifies targeted protein degradation, but therapeutic success depends on sufficient DCAF15 expression, and cutting RBM39 levels can have widespread effects due to its role in mRNA processing[3][5][1][2][4].

Other names

CRL4-DCAF15–RBM39 complexDCAF15–RBM39–DDB1–DDA1 complex

Small molecule (aryl sulfonamide) acts as a molecular glue, inducing an interaction between DCAF15 and RBM39 Recruitment of RBM39 to CRL4-DCAF15 leads to its ubiquitination and proteasome-dependent degradation[2][3][1]