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

Author(s): Czabotar, PE; Lee, EF; van Delft, MF; Day, CL; Smith, BJ; Huang, DCS; Fairlie, WD; Hinds, MG; Colman, PM;
Details: 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
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.
Publisher: NATL ACAD SCIENCES
Keywords: PROGRAMMED CELL-DEATH; BCL-2 FAMILY; BH3-ONLY PROTEINS; APOPTOSIS; SURVIVAL; COMPLEX; INHIBITOR; DIFFERENTIATION; MUTAGENESIS; LYMPHOCYTES
Publisher's Version: https://doi.org/10.1073/pnas.0701297104
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2007-04-10 12:00:00