Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis.
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.
Zha
J
J
Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Departments of Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA.
Weiler
S
S
Oh
K J
KJ
Wei
M C
MC
Korsmeyer
S J
SJ
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D019169:Jurkat Cells; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D019814:Myristic Acid / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C494815:Bid protein, mouse; D002352:Carrier Proteins; D003574:Cytochrome c Group; D008081:Liposomes; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D019814:Myristic Acid; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases