期刊
EMBO JOURNAL
卷 32, 期 16, 页码 2204-2216出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2013.133
关键词
autophagy; Mdm2; XIAP
资金
- Ministry of Science and Technology of China [2010CB912804, 2011CB966302]
- National Natural Science Foundation of China [31030046, 31171316]
- Chinese Academy of Sciences [XDA01020104]
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.
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