Calpain-dependent cleavage of cain/cabin1 activates calcineurin to mediate calcium-triggered cell death.

ABSTRACT: Cain/cabin1 is an endogenous inhibitor of calcineurin (Cn), a calcium-dependent serine/threonine phosphatase involved in various cellular functions including apoptosis. We show here that during apoptosis cain/cabin1 is cleaved by calpain at the carboxyl terminus to generate a cleavage product with a molecular mass of 32 kDa as a necessary step leading to Cn-mediated cell death. Mouse cain/cabin1 was identified from a thymus cDNA library by an in vitro substrate-screening assay with calpain. Exposure of Jurkat cells to the calcium ionophore, induced cain/cabin1 cleavage and cell death, accompanied by activation of calpain and Cn. The calpain inhibitors, calpeptin and zLLY, suppressed both -induced cain/cabin1 cleavage and Cn activation, indicating that Cn activation and cain/cabin1 cleavage

SUBMITTER: Kim MJ 

PROVIDER: S-EPMC125047 | biostudies-literature | 2002 Jul

REPOSITORIES: biostudies-literature