Discovery of PROTACs recruiting the E3 ligase CHIP

This is the authors' abstract. We don't add key points for this paper.

ubiquitylation assay revealed that CHIP induced not only the lysine (K) 48-linked polyubiquitin (poly-Ub) chain, which is a typical proteasome degradation signal, but also the K63 linkage. Furthermore, it induces the proteasome-dependent degradation of HaloTag protein and endogenous bromodomain-containing protein 4 (BRD4). Thus, we successfully expanded the E3 ligase toolbox for PROTACs. These new PROTACs using CHIP, which induce non-canonical proteasome degradation signals containing a mixed linkage of poly-Ub chains on the target protein, can be applied to the degradation of other proteins, especially disease-related proteins.