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Notch inhibits apoptosis by direct interference with XIAP ubiquitination and degradation
Author(s) -
Liu WenHsien,
Hsiao HueyWen,
Tsou WenI,
Lai MingZong
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601611
Subject(s) - xiap , biology , ubiquitin , apoptosis , microbiology and biotechnology , inhibitor of apoptosis , rna interference , degradation (telecommunications) , interference (communication) , cancer research , genetics , caspase , programmed cell death , gene , telecommunications , rna , channel (broadcasting) , computer science
The physiological activity of Notch is a function of its ability to increase survival in many cell types. Several pathways have been shown to contribute to the survival effect of Notch, but the exact mechanism of Notch action is not completely understood. Here we identified that the regulation of cell survival by Notch intracellular domain could partly be attributed to a selective increase of X‐linked inhibitor of apoptosis protein (XIAP). We further found that Notch intracellular domain inhibited the degradation of XIAP during apoptosis. The transactivation domain of Notch interacted directly with the RING region of XIAP to block the binding of E2 and prevent the in vivo and in vitro ubiquitination of XIAP. This antiapoptotic activity of Notch was abolished when XIAP was knocked down. Our results reveal a novel mechanism for Notch‐selective suppression of apoptosis through an increase in the stability of a key antiapoptotic protein, XIAP.