Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 15, Pages 6217-6222Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0701297104
Keywords
apoptosis; Bim; Noxa; crystallography
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Funding
- NCI NIH HHS [R01 CA080188, CA80188] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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Apoptosis is held in check by prosurvival proteins of the Bcl-2 family. The distantly related BH3-only proteins bind to and antagonize them, thereby promoting apoptosis. Whereas binding of the BH3-only protein Noxa to prosurvival Mcl-1 induces Mcl-1 degradation by the proteasome, binding of another BH3-only ligand, Bim, elevates Mcl-1 protein levels. We compared the three-dimensional structures of the complexes formed between BH3 peptides of both Bim and Noxa, and we show that a discrete C-terminal sequence of the Noxa BH3 is necessary to instigate Mcl-1 degradation.
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