DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9

Author(s): Ekert, PG; Silke, J; Hawkins, CJ; Verhagen, AM; Vaux, DL;
Details: Publication Year 2001-02-05,Volume 152,Issue #3,Page 483-490
Journal Title: JOURNAL OF CELL BIOLOGY
Publication Type: Journal Article
Abstract: MIHA is an inhibitor of apoptosis protein (IAP) that can inhibit cell death by direct interaction with caspases, the effector proteases of apoptosis. DIABLO is a mammalian protein that can bind to IAPs and antagonize their antiapoptotic effect, a function analogous to that of the proapoptotic Drosophila molecules, Grim, Reaper, and HID. Here. we show that after UV radiation, MIHA prevented apoptosis by inhibiting caspase 9 and caspase 3 activation. Unlike Bcl-2, MIHA functioned after release of cytochrome c and DIABLO from the mitochondria and was able to bind to both processed caspase 9 and processed caspase 3 to prevent feedback activation of their zymogen forms. Once released into the cytosol, DIABLO bound to MIHA and disrupted its association with processed caspase 9, thereby allowing caspase 9 to activate caspase 3, resulting in apoptosis.
Publisher: ROCKEFELLER UNIV PRESS
Keywords: CELL-DEATH; MAMMALIAN-CELLS; SACCHAROMYCES-CEREVISIAE; BACULOVIRUS INHIBITOR; CYTOCHROME-C; IN-VIVO; PROTEINS; IAP; DOMAIN; GENES
Publisher's Version: https://doi.org/10.1083/jcb.152.3.483
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2001-02-05 12:00:00