DDB1-and-CUL4-associated factor 16 (DCAF16) (DCAF16)

DDB1-and-CUL4-associated factor 16 (DCAF16) is a substrate receptor for the Cullin-RING E3 ubiquitin ligase 4 (CRL4) complex, primarily localized in the nucleus (Zhang et al., 2019, Nature Chemical Biology). It has gained significant attention in the field of targeted protein degradation (TPD) as a versatile E3 ligase recruiter for the development of proteolysis-targeting chimeras (PROTACs) and molecular glues (Noman et al., 2021, Frontiers in Cell and Developmental Biology). Unlike the more commonly used cereblon (CRBN) or von Hippel-Lindau (VHL) ligases, DCAF16 is particularly effective at mediating the degradation of nuclear proteins due to its constitutive nuclear localization (UniProt Q9NXF7). Small molecules, often featuring electrophilic groups, can covalently bind to cysteine residues on DCAF16, facilitating the formation of a ternary complex with a target protein of interest (Zhang et al., 2019). This proximity leads to the polyubiquitination of the target protein and its subsequent degradation by the 26S proteasome. DCAF16-mediated degradation offers a strategy to expand the "degradable" proteome, especially for targets that are resistant to other E3 ligases or require nuclear-specific recruitment (Burslem & Crews, 2020, ChemBioChem).

Other names

C1orf189DDB1- and CUL4-associated factor 16DCAF16-mediated ternary complex

Targeted protein degradation via the recruitment of a target protein to the CRL4-DCAF16 E3 ligase complex for ubiquitination and subsequent proteasomal degradation.