Recombinant antibodies inhibit enzymatic activity of the E3 ubiquitin ligase CHIP via multiple mechanisms.

ABSTRACT: Carboxyl-terminus of Hsp70-Interacting Protein (CHIP) is an E3 ubiquitin ligase that marks misfolded substrates for degradation. Hyper-activation of CHIP has been implicated in multiple diseases, including cystic fibrosis and cancer, suggesting that it may be a potential drug target. However, there are few tools available for exploring this possibility. Moreover, the best ways of inhibiting CHIP's function are not obvious, as this complex protein is composed of a tetratricopeptide repeat (TPR) domain, a U-box domain, and a coiled-coil domain that mediates homodimerization. To probe the structure and function of CHIP, we report an antibody panning campaign that yielded six recombinant Fabs with affinity for CHIP. Interestingly, these antibodies varied in their binding site(s) and impact on

SUBMITTER: Chung DH 

PROVIDER: S-EPMC11883360 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature