Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG

Chengyu Liang, Pinghui Feng, Bonsu Ku, Iris Dotan, Dan Canaani, Byung Ha Oh, Jae U. Jung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

888 Scopus citations


Autophagy, the degradation of cytoplasmic components, is an evolutionarily conserved homeostatic process involved in environmental adaptation, lifespan determination and tumour development. The tumor suppressor Beclin1 is part of the PI(3) kinase class III (PI(3)KC3) lipid-kinase complex that induces autophagy. The autophagic activity of the Beclin1-PI(3)KC3 complex, however, is suppressed by Bcl-2. Here, we report the identification of a novel coiled-coil UV irradiation resistance-associated gene (UVRAG) as a positive regulator of the Beclin1-PI(3)KC3 complex. UVRAG, a tumour suppressor candidate that is monoallelically mutated at high frequency in human colon cancers, associates with the Beclin1-Bcl-2-PI(3)KC3 multiprotein complex, where UVRAG and Beclin1 interdependently induce autophagy. UVRAG-mediated activation of the Beclin1-PI(3)KC3 complex promotes autophagy and also suppresses the proliferation and tumorigenicity of human colon cancer cells. These results identify UVRAG as an essential component of the Beclin1-PI(3)KC3 lipid kinase complex that is an important signalling checkpoint for autophagy and tumour-cell growth.

Original languageEnglish
Pages (from-to)688-698
Number of pages11
JournalNature Cell Biology
Issue number7
StatePublished - Jul 2006


FundersFunder number
Creative Research Initiative of Korea Ministry of Science and Technology
National Cancer InstituteR01CA091819
U.S. Public Health ServiceCA82057, RR00168, CA31363, CA106156


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