Structural insights into the degradation of Mcl-1 induced by BH3 domains
- Czabotar, PE; Lee, EF; van Delft, MF; Day, CL; Smith, BJ; Huang, DCS; Fairlie, WD; Hinds, MG; Colman, PM;
Publication Year 2007-04-10, Volume 104, Issue #15, Page 6217-6222
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- 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.
- NATL ACAD SCIENCES
- PROGRAMMED CELL-DEATH; BCL-2 FAMILY; BH3-ONLY PROTEINS; APOPTOSIS; SURVIVAL; COMPLEX; INHIBITOR; DIFFERENTIATION; MUTAGENESIS; LYMPHOCYTES
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2007-04-10 12:00:00Last Modified: 0001-01-01 12:00:00