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Science 1 December 2000:
Vol. 290. no. 5497, pp. 1761 - 1765
DOI: 10.1126/science.290.5497.1761
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Reports

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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