title: SVIP induces localization of p97/VCP to the plasma and lysosomal membranes and regulates autophagy.
abstract: The small p97/VCP-interacting protein (SVIP) functions as an inhibitor of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. Here we show that overexpression of SVIP in HeLa cells leads to localization of p97/VCP at the plasma membrane, intracellular foci and juxtanuclear vacuoles. The p97/VCP-positive vacuolar structures colocalized or associated with LC3 and lamp1, suggesting that SVIP may regulate autophagy. In support of this possibility, knockdown of SVIP diminished, whereas overexpression of SVIP enhanced LC3 lipidation. Surprisingly, knockdown of SVIP reduced the levels of p62 protein at least partially through downregulation of its mRNA, which was accompanied by a decrease in starvation-induced formation of p62 bodies. Overexpression of SVIP, on the other hand, increased the levels of p62 protein and enhanced starvation-activated autophagy as well as promoted sequestration of polyubiquitinated proteins and p62 in autophagosomes. These results suggest that SVIP plays a regulatory role in p97 subcellular localization and is a novel regulator of autophagy.
authors: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun, People's Republic of China.
authors: Yang
authors: Y
authors: Wang
authors: Petek
authors: P
authors: Ballar
authors: Yongwang
authors: Y
authors: Zhong
authors: Xuebao
authors: X
authors: Zhang
authors: Chao
authors: C
authors: Liu
authors: Ying-Jiu
authors: YJ
authors: Zhang
authors: Mervyn J
authors: MJ
authors: Monteiro
authors: Jun
authors: J
authors: Li
authors: Shengyun
authors: S
authors: Fang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D028044:Phosphate-Binding Proteins; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D054875:Ubiquitination; D014617:Vacuoles / Q000378:metabolism; D000074405:Valosin Containing Protein; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D049452:Green Fluorescent Proteins; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D028044:Phosphate-Binding Proteins; D011993:Recombinant Fusion Proteins; D000071456:Sequestosome-1 Protein; D000074405:Valosin Containing Protein; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C477012:MAP1LC3A protein, human; C099718:SQSTM1 protein, human; C569017:SVIP protein, human; C569020:SVIP protein, mouse; C000614178:VCP protein, human; C000614179:Vcp protein, mouse