Regulation of Beclin 1 in autophagy.
Class III phosphatidylinositol 3-kinase (PI3KC3) plays a pleiotropic role in autophagy and protein sorting pathways. The human core complex of PI3KC3 consists of three major components including PI3KC3/hVps34, p150 and Beclin 1. How the specificity of PI3KC3 complex is derived towards autophagy is not clear. Utilizing a sequential affinity purification ... coupled with mass spectrometry approach, we have successfully purified a human Beclin 1 complex and cloned a novel protein we called Barkor (Beclin 1-associated autophagy-related key regulator). The function of Barkor in autophagy has been manifested in several assays, including stress-induced LC3 lipidation, autophagosome formation and Salmonella typhimurium amplification. Mechanistically, Barkor competes with UV radiation resistance associated gene product (UVRAG) for interaction with Beclin 1, and orients Beclin 1 to autophagosomes. Barkor shares considerable sequence homology with Atg14 in yeast, representing an evolutionary conserved autophagy specific regulatory step in early autophagosome formation.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Apoptosis Regulatory Proteins, Autophagy, Cell Line, Cell Membrane, Cell Polarity, Humans, Membrane Proteins, Models, Biological, Neoplasms, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Tumor Suppressor Proteins
1-Phosphatidylinositol 3-Kinase, Apoptosis Regulatory Proteins, Autophagy, Cell Line, Cell Membrane, Cell Polarity, Humans, Membrane Proteins, Models, Biological, Neoplasms, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Tumor Suppressor Proteins
Autophagy
Date: Jul. 01, 2009
PubMed ID: 19372752
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