Determination of cell survival by RING-mediated regulation of inhibitor of apoptosis (IAP) protein abundance

Author(s): Silke, J; Kratina, T; Chu, D; Ekert, PG; Day, CL; Pakusch, M; Huang, DCS; Vaux, DL;
Details: Publication Year 2005-11-08,Volume 102,Issue #45,Page 16182-16187
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type: Journal Article
Abstract: Inhibitor of apoptosis (IAP) proteins, which bind to caspases via their baculoviral IAP repeat domains, also bear RING domains that enable them to promote ubiquitylation of themselves and other interacting proteins. Here we show that the RING domain of cIAP1 allows it to bind directly to the RING of X-linked IAP, causing its ubiquitylation and degradation by the proteasome, thus revealing a mechanism by which IAPs can regulate their abundance. Expression of a construct containing the RING of cellular IAP1 was able to deplete melanoma cells of endogenous X-linked IAP, promoted apoptosis, and also markedly reduced their donogenicity when treated with cisplatin. Cross control of protein levels by RING domains may therefore enable their levels to be manipulated therapeutically.
Publisher: NATL ACAD SCIENCES
Keywords: UBIQUITIN LIGASE ACTIVITY; PROTEASOMAL DEGRADATION; LINKED INHIBITOR; IN-VITRO; BCL-W; XIAP; C-IAP1; SMAC/DIABLO; CASPASES; COMPLEX
Publisher's Version: https://doi.org/10.1073/pnas.0502828102
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2005-11-08 12:00:00