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XIAP inhibits autophagy via XIAP‐Mdm2‐p53 signalling

Xing Huang, Zhengsheng Wu, Yide Mei, Mian Wu

Author Affiliations

  1. Xing Huang1,,
  2. Zhengsheng Wu2,,
  3. Yide Mei*,1 and
  4. Mian Wu*,1
  1. 1 Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China
  2. 2 Department of pathology, Anhui Medical University, Hefei China
  1. *Corresponding authors. Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, 443 Huang‐Shan Road, Hefei, Anhui 230027, China. Tel./Fax: 86 551 63600921; E-mail: meiyide{at}ustc.edu.cnHefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, 443 Huang‐Shan Road, Hefei, Anhui 230027, China. Tel.: 86 551 3607324; Fax: 86 551 3606264; E-mail: wumian{at}ustc.edu.cn
  1. These authors contributed equally to this work.

Abstract

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.

There is a Have you seen? (August 2013) associated with this Article.

  • Received December 25, 2012.
  • Accepted May 16, 2013.

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