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Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6217-22. Epub 2007 Mar 27.

Structural insights into the degradation of Mcl-1 induced by BH3 domains.

Author information

1
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.

Abstract

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.

PMID:
17389404
PMCID:
PMC1851040
DOI:
10.1073/pnas.0701297104
[Indexed for MEDLINE]
Free PMC Article

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