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.
Sun
Qiming
Q
University of California, Berkeley, Department of Molecular & Cell Biology, Berkeley, CA 94720, USA.
Fan
Weiliang
W
Zhong
Qing
Q
D051017:Apoptosis Regulatory Proteins / Q000302:isolation & purification / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D006801:Humans; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; C491997:BECN1 protein, human; C408122:UVRAG protein, human