UVRAG AUTOPHAGIC TUMOR SUPPRESSOR PROTEIN

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Autophagy, the degradation of cytoplasmic components, is an evolutionarily conserved homeostatic process involved in environmental adaptation, lifespan determination, and tumor development. The tumor suppressor, Beclin1, is part of the PI3 kinase class III (PI3KC3) lipid kinase complex that induces autophagy. The autophagic activity of Beclin1-PI3KC3 complex, however, is suppressed by Bcl-2. Here, we report the identification of a novel coiled-coil UVRAG tumor suppressor candidate as a positive regulator of Beclin1-PI3KC3 complex. UVRAG, which is monoallelically mutated at high frequency in human colon cancers, associates with the Beclin1-Bcl-2-PI3KC3 multiprotein complex, where UVRAG and Beclin1 interdependently induce autophagy. UVRAG-mediated activation of Beclin1-PI3KC3 complex not only promotes autophagy but also suppresses the proliferation and tumorigenicity of human colon cancer cells.