Article abstract
Nature Cell Biology 8, 688 - 698 (2006)
Published online: 25 June 2006 | doi:10.1038/ncb1426
Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG
Chengyu Liang1, Pinghui Feng1, Bonsu Ku2, Iris Dotan3, Dan Canaani3, Byung-Ha Oh2 & Jae U. Jung1
Abstract
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.
- Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Primate Research Center, Harvard Medical School, 1 Pine Hill Drive, Southborough, MA 01772, USA.
- Center for Biomolecular Recognition, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, 790-784, Korea.
- Department of Biochemistry, Tel-Aviv University, Tel-Aviv 69978, Israel.
Correspondence to: Jae U. Jung1 e-mail: jae_jung@hms.harvard.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
UVRAG reveals its second natureNature Cell Biology News and Views (01 Jul 2008)
p53: The Janus of autophagy?Nature Cell Biology News and Views (01 Jun 2008)
See all 5 matches for News And ViewsRESEARCH
Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesisNature Cell Biology Article (01 Oct 2007)
Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic traffickingNature Cell Biology Article (01 Jul 2008)
See all 27 matches for Research
