CAPN15 is a non-proteasomal, ubiquitin-directed calpain protease that regulates cell adhesion by cleaving E-cadherin.

ABSTRACT: CAPN15, a member of the calpain protease family, contains a unique N-terminal region with five Zn²⁺-finger domains, including two ubiquitin-binding Npl4-type Zn²⁺-finger domains. However, the role of these domains in CAPN15 function remains unknown. In this study, we show that CAPN15 functions as a non-proteasomal, ubiquitin-directed protease, regulating cell surface E-cadherin. In cultured epithelial cells, CAPN15 KO resulted in densely packed morphology accompanied by the accumulation of cell surface E-cadherin, suggesting an increased cell adhesion. This defect was rescued by expressing WT CAPN15, but not protease-inactive or ubiquitin-binding-deficient CAPN15. CAPN15 recognizes the ubiquitinated E-cadherin-catenin complex through its N-terminal Zn²⁺-fin

SUBMITTER: Noguchi A 

PROVIDER: S-EPMC12805371 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature