TY - JOUR
T1 - Ca2+-Induced Apoptosis Through Calcineurin Dephosphorylation of BAD
AU - Wang, Hong Gang
AU - Pathan, Nuzhat
AU - Ethell, Iryna M.
AU - Krajewski, Stanislaw
AU - Yamaguchi, Yu
AU - Shibasaki, Futoshi
AU - McKeon, Frank
AU - Bobo, Tanya
AU - Franke, Thomas F.
AU - Reed, John C.
PY - 1999/4/9
Y1 - 1999/4/9
N2 - 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.
AB - 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.
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U2 - 10.1126/science.284.5412.339
DO - 10.1126/science.284.5412.339
M3 - Article
C2 - 10195903
AN - SCOPUS:0033537768
SN - 0036-8075
VL - 284
SP - 339
EP - 343
JO - Science
JF - Science
IS - 5412
ER -