XIAP inhibits autophagy via XIAP‐Mdm2‐p53 signalling. (7th June 2013)

• Record Type: Journal Article
• Authors: Huang, Xing; Wu, Zhengsheng; Mei, Yide; Wu, Mian
• Is Part Of: EMBO journal. Volume 32:Number 16(2013)
• Page Start: 2204
• Page End: 2216
• Publication Date: 2013-06-07
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.1038/emboj.2013.133
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The primary role of autophagy is adaption to starvation. However, increasing evidence suggests that autophagy inhibition also plays an important role in tumorigenesis. Upregulation of X‐linked inhibitor of apoptosis (XIAP) has been associated to a variety of human cancers, yet the underlying mechanisms remain obscure. Here, we report that XIAP suppresses autophagy by exerting a previously unidentified ubiquitin E3 ligase activity towards Mdm2, which is a negative regulator of p53. XIAP controls serum starvation‐induced autophagy downstream of the PI3K/Akt pathway. In mouse models, inhibition of autophagy by XIAP promotes tumorigenecity of HCT116 cells. XIAP‐mediated autophagy inhibition is also largely validated in clinical tumour samples. These findings reveal a novel XIAP‐Mdm2‐p53 pathway that mediates the inhibition of autophagy, by which XIAP may contribute to tumorigenesis.</p> </abstract>