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Science 290 (5497): 1761-1765

Copyright © 2000 by the American Association for the Advancement of Science

Posttranslational N-Myristoylation of BID as a Molecular Switch for Targeting Mitochondria and Apoptosis

Jiping Zha,* Solly Weiler,* Kyoung Joon Oh, Michael C. Wei, Stanley J. Korsmeyerdagger

Many apoptotic molecules relocate subcellularly in cells undergoing apoptosis. The pro-apoptotic protein BID underwent posttranslational (rather than classic cotranslational) N-myristoylation when cleavage by caspase 8 caused exposure of a glycine residue. N-myristoylation enabled the targeting of a complex of p7 and myristoylated p15 fragments of BID to artificial membranes bearing the lipid composition of mitochondria, as well as to intact mitochondria. This post-proteolytic N-myristoylation serves as an activating switch, enhancing BID-induced release of cytochrome c and cell death.

Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Departments of Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: stanley_korsmeyer{at}dfci.harvard.edu


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Protein N-myristoylation: Critical Role in Apoptosis and Salt Tolerance.
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Sci. STKE 2000, pe1
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Caspase-2-induced Apoptosis Is Dependent on Caspase-9, but Its Processing during UV- or Tumor Necrosis Factor-dependent Cell Death Requires Caspase-3.
G. Paroni, C. Henderson, C. Schneider, and C. Brancolini (2001)
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BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia.
N. Plesnila, S. Zinkel, D. A. Le, S. Amin-Hanjani, Y. Wu, J. Qiu, A. Chiarugi, S. S. Thomas, D. S. Kohane, S. J. Korsmeyer, et al. (2001)
PNAS 98, 15318-15323
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A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast.
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J. Cell Biol. 155, 725-732
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ARL2 and BART Enter Mitochondria and Bind the Adenine Nucleotide Transporter.
J. D. Sharer, J. F. Shern, H. Van Valkenburgh, D. C. Wallace, and R. A. Kahn (2002)
Mol. Biol. Cell 13, 71-83
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