SMARCA2/4 degradation tails mediate recruitment of two different E3 ligases 

ABSTRACT: In this work, we characterise novel SMARCA2/4 degraders using a robust cell biology and structural workflow and reveal for the first time, the recruitment of two E3 ligase substrate receptors: FBXO22 and DCAF16 by the same degradation tail. Furthermore, we were able to chemically fine-tune this dual ligase dependency dialling out DCAF16 providing insights into the mechanisms for DCAF16 and FBXO22 covalent recruitment. Dual ligase recruitment may serve to overcome E3 ligase acquired resistance that may feature with clinical use of degraders.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney

SUBMITTER: Gajanan Sathe  

LAB HEAD: Alessio Ciulli

PROVIDER: PXD065445 | Pride | 2026-05-16

REPOSITORIES: Pride