Calpain activity is negatively regulated by a KCTD7-Cullin-3 complex via non-degradative ubiquitination.

ABSTRACT: Calpains are a class of non-lysosomal cysteine proteases that exert their regulatory functions via limited proteolysis of their substrates. Similar to the lysosomal and proteasomal systems, calpain dysregulation is implicated in the pathogenesis of neurodegenerative disease and cancer. Despite intensive efforts placed on the identification of mechanisms that regulate calpains, however, calpain protein modifications that regulate calpain activity are incompletely understood. Here we show that calpains are regulated by KCTD7, a cytosolic protein of previously uncharacterized function whose pathogenic mutations result in epilepsy, progressive ataxia, and severe neurocognitive deterioration. We show that KCTD7 works in complex with Cullin-3 and Rbx1 to execute atypical, non-degradative ubiquit

SUBMITTER: Sharma J 

PROVIDER: S-EPMC10038992 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature