Ca2+-Induced Apoptosis Through Calcineurin Dephosphorylation of BAD

Hong Gang Wang, Nuzhat Pathan, Iryna M. Ethell, Stanislaw Krajewski, Yu Yamaguchi, Futoshi Shibasaki, Frank McKeon, Tanya Bobo, Thomas F. Franke, John C. Reed

Research output: Contribution to journalArticlepeer-review

922 Scopus citations

Abstract

The Ca2+-activated protein phosphatase calcineurin induces apoptosis, but the mechanism is unknown. Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xLand promoting apoptosis. The Ca2+-induced dephosphorylation of BAD correlated with its dissociation from 14-3-3 in the cytosol and translocation to mitochondria where Bcl-xLresides. In hippocampal neurons, L-glutamate, an inducer of Ca2+influx and calcineurin activation, triggered mitochondrial targeting of BAD and apoptosis, which were both suppressible by coexpression of a dominant-inhibitory mutant of calcineurin or pharmacological inhibitors of this phosphatase. Thus, a Ca2+-inducible mechanism for apoptosis induction operates by regulating BAD phosphorylation and localization in cells.

Original languageEnglish (US)
Pages (from-to)339-343
Number of pages5
JournalScience
Volume284
Issue number5412
DOIs
StatePublished - Apr 9 1999

All Science Journal Classification (ASJC) codes

  • General

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