CABIN-1, A NEGATIVE REGULATOR FOR CALCINEURIN SIGNALING IN T-LYMPHOCYTES

Calcineurin plays a pivotal role in the T cell receptor (TCR)-mediated signal transduction pathway and serves as a common target for the imm unosuppressants FK506 and cyclosporin A. We report the identification of a novel endogenous calcineurin binding protein named Cabin 1 that i nhibits calcineurin-mediated signal transduction. The interaction betw een Cabin 1 and calcineurin is dependent on PKC activation. Overexpres sion of Cabin 1 or its N-terminal truncation mutants inhibits the tran scriptional activation of calcineurin-responsive elements in the inter leukin-2 promoter and blocks dephosphorylation of NF-AT upon T cell ac tivation. These results suggest a negative regulatory role for Cabin 1 in calcineurin signaling and provide a possible mechanism of feedback inhibition of TCR signaling through cross-talk between protein kinase s and calcineurin.