Ca ²⁺ -Induced Apoptosis Through Calcineurin Dephosphorylation of BAD

• Hong-Gang Wang

  The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

• Nuzhat Pathan

  The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

• Iryna M. Ethell

  The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

• Stanislaw Krajewski

  The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

• Yu Yamaguchi

  The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

• Futoshi Shibasaki

  Department of Cell Biology, Harvard University, School of Medicine, Boston, MA 02115, USA.

• Frank McKeon

  Department of Cell Biology, Harvard University, School of Medicine, Boston, MA 02115, USA.

• Tanya Bobo

  Columbia University, Department of Pharmacology, 630 West 168 Street, New York, NY 10032, USA.

• Thomas F. Franke

  Columbia University, Department of Pharmacology, 630 West 168 Street, New York, NY 10032, USA.

• John C. Reed

  The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

抄録

The Ca 2+ -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-x L and promoting apoptosis. The Ca 2+ -induced dephosphorylation of BAD correlated with its dissociation from 14-3-3 in the cytosol and translocation to mitochondria where Bcl-x L resides. In hippocampal neurons, l -glutamate, an inducer of Ca 2+ 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 Ca 2+ -inducible mechanism for apoptosis induction operates by regulating BAD phosphorylation and localization in cells.

収録刊行物

• Science

  Science 284 (5412), 339-343, 1999-04-09

  American Association for the Advancement of Science (AAAS)

キーワード

• Multidisciplinary

詳細情報

• CRID: 1362544419665702528
• NII論文ID: 80011039459
• DOI: 10.1126/science.284.5412.339
• ISSN: 10959203
• ISSN: 00368075
• ISSN: http://id.crossref.org/issn/00368075
• Web Site: https://www.science.org/doi/pdf/10.1126/science.284.5412.339
• データソース種別:
  • Crossref
  • CiNii Articles