PIASy stimulates HIF1α SUMOylation and negatively regulates HIF1α activity in response to hypoxia
PIASy stimulates HIF1α SUMOylation and negatively regulates HIF1α activity in response to hypoxia
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DOI：
10.1038/onc.2010.297
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发表时间：
2010-10-01
期刊：
影响因子：
8
通讯作者：
Cheng, J.
中科院分区：
文献类型：
--
作者：
Kang, X.;Li, J.;Cheng, J.
Hypoxia-inducible factor-1 alpha (HIF1 alpha) is a crucial regulator of the cellular response to hypoxia through its regulation of genes that control erythropoiesis, angiogenesis and anaerobic metabolism. We have previously shown that HIF1 alpha stability is regulated by SUMOylation under the hypoxic condition. However, how HIF1 alpha became SUMOylated during hypoxia is still unknown. In this study we identify PIASy as a specific E3 ligase for hypoxia-induced HIF1 alpha SUMOylation. Hypoxia promotes translocation of HIF1 alpha to the nucleus to facilitate its binding to PIASy, enabling the conjugation of HIF1 alpha by SUMO1. We further show that PIASy negatively regulates hypoxia-induced HIF1 alpha stability and transactivation. Knocking down PIASy increases the angiogenic activity of endothelial cells. Moreover, we show an inverse relationship between expression of PIASy and tumor angiogenesis in colon cancer. Thus, we define an important role of PIASy in hypoxia signaling through promoting HIF1 alpha SUMOylation. Oncogene (2010) 29, 5568-5578; doi:10.1038/onc.2010.297; published online 26 July 2010
