UVRAG AUTOPHAGIC TUMOR SUPPRESSOR PROTEIN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 自噬是细胞质成分的降解，是一种进化上保守的稳态过程，涉及环境适应、寿命决定和肿瘤发展。肿瘤抑制因子Beclin 1是PI 3激酶III类（PI 3 KC 3）脂质激酶复合物的一部分，可诱导自噬。然而，Beclin 1-PI 3 KC 3复合物的自噬活性受到Bcl-2的抑制。在这里，我们报告了一种新的卷曲螺旋UVRAG肿瘤抑制候选人的Beclin 1-PI 3 KC 3复合物的正调节剂的鉴定。UVRAG在人类结肠癌中以高频率单等位基因突变，与Beclin 1-Bcl-2-PI 3 KC 3多蛋白复合物相关，其中UVRAG和Beclin 1相互依赖地诱导自噬。UVRAG介导的Beclin 1-PI 3 KC 3复合物的活化不仅促进自噬，而且抑制人结肠癌细胞的增殖和致瘤性。

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.