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  • The EMBO Journal (2007) 26, 1660 - 1669
  • doi:10.1038/sj.emboj.7601611

Published online: 22 February 2007

Notch inhibits apoptosis by direct interference with XIAP ubiquitination and degradation

Wen-Hsien Liu1, Huey-Wen Hsiao1,2, Wen-I Tsou1 and Ming-Zong Lai1,2,3

  1. Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, ROC
  2. Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, ROC
  3. Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan, ROC

Correspondence to:

Ming-Zong Lai, Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, ROC. Tel.: +886 2 2789 9236; Fax: +886 2 2782 6085; E-mail: mblai@imb.sinica.edu.tw

Received 21 August 2006; Accepted 25 January 2007

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.

  • Keywords:

    • apoptosis,
    • Notch,
    • ubiquitination,
    • XIAP
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