title: Binding Rubicon to cross the Rubicon.
abstract: Beclin 1 is an antitumor protein, required for mammalian autophagy, but its precise molecular function is poorly understood. Mass spectrometry analysis reveals that two novel proteins, Atg14L and Rubicon, associate with Beclin 1, together with a known Beclin 1-binding protein, UVRAG. The interactions of Atg14L and UVRAG with the Beclin 1-Vps34 (class III PI3-kinase)-Vps15 core complex are mutually exclusive; Rubicon associates with a subpopulation of UVRAG-containing complexes. The Atg14L complex, which positively regulates autophagy at an early step, localizes to the phagophore/isolation membrane, autophagosome and endoplasmic reticulum. In contrast, the Rubicon-UVRAG complex localizes to the late endosome/lysosome and negatively regulates both autophagy at a later step and the endocytic pathway. Thus, the Beclin 1-Vps34-Vps15 complex functions in autophagy and the endocytic pathway, but its function in a given context depends on the identity of its interacting subunits.
authors: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors: Kohichi
authors: K
authors: Matsunaga
authors: Takeshi
authors: T
authors: Noda
authors: Tamotsu
authors: T
authors: Yoshimori
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010588:Phagosomes / Q000378:metabolism; D011485:Protein Binding; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D025521:Tumor Suppressor Proteins