Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases.

ABSTRACT: Protein-protein interactions between E3 ubiquitin ligases and protein termini help shape the proteome. These interactions are sensitive to proteolysis, which alters the ensemble of cellular N and C termini. Here we describe a mechanism wherein caspase activity reveals latent C termini that are then recognized by the E3 ubiquitin ligase CHIP. Using expanded knowledge of CHIP's binding specificity, we predicted hundreds of putative interactions arising from caspase activity. Subsequent validation experiments confirmed that CHIP binds the latent C termini at tau^D421 and caspase-6^D179. CHIP binding to tau^D421, but not tau^FL, promoted its ubiquitination, while binding to caspase-6^D179 mediated ubiquitin-independent inhibition. Given that ca

SUBMITTER: Ravalin M 

PROVIDER: S-EPMC6693490 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature