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http://purl.uniprot.org/citations/33783314http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33783314http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33783314http://www.w3.org/2000/01/rdf-schema#comment"MOAP1 (modulator of apoptosis 1) is a BAX-binding protein tightly regulated by the ubiquitin-proteasome system. Apoptotic stimuli stabilize MOAP1 protein and facilitate its interaction with BAX to promote apoptosis. Here we show that in contrast to being resistant to apoptotic stimuli, MOAP1-deficient cells are hypersensitive to cell death mediated by starvation rendered by EBSS treatment. MOAP1-deficient cells exhibited impairment in macroautophagy/autophagy signaling induced by EBSS. Mechanistic analysis revealed that MOAP1-deficient cells had no notable defect in the recruitment of the pre-autophagosomal phosphatidylinositol-3-phosphate (PtdIns3P)-binding proteins, ZFYVE1/DFCP1 and WIPI2, nor in the LC3 lipidation mechanism regulated by the ATG12-ATG5-ATG16L1 complex upon EBSS treatment. Interestingly, MOAP1 is required for facilitating efficient closure of phagophore in the EBSS-treated cells. Analysis of LC3-positive membrane structures using Halo-tagged LC3 autophagosome completion assay showed that predominantly unclosed phagophore rather than closed autophagosome was present in the EBSS-treated MOAP1-deficient cells. The autophagy substrate SQSTM1/p62, which is normally contained within the enclosed autophagosome under EBSS condition, was also highly sensitive to degradation by proteinase K in the absence of MOAP1. MOAP1 binds LC3 and the binding is critically dependent on a LC3-interacting region (LIR) motif detected at its N-terminal region. Re-expression of MOAP1, but not its LC3-binding defective mutant, MOAP1-LIR, in the MOAP1-deficient cells, restored EBSS-induced autophagy. Together, these observations suggest that MOAP1 serves a distinct role in facilitating autophagy through interacting with LC3 to promote efficient phagophore closure during starvation.Abbreviations: CQ: Chloroquine; EBSS: Earle's Balanced Salt Solution; GABARAP: Gamma-Amino Butyric Acid Receptor Associated Protein; IF: Immunofluorescence; IP: Immunoprecipitation; LAMP1: Lysosomal-Associated Membrane Protein 1; LIR: LC3-Interacting Region; MAP1LC3/LC3: Microtubule Associated Protein 1 Light Chain 3; MEF: Mouse Embryonic Fibroblast; MOAP1: Modulator of Apoptosis 1; PE: Phosphatidylethanolamine; PtdIns3K: class III PtdIns3K complex I; PtdIns3P: Phosphatidylinositol-3-phosphate; STX17: Syntaxin 17; ULK1: unc-51 like autophagy activating kinase 1."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.org/dc/terms/identifier"doi:10.1080/15548627.2021.1896157"xsd:string
http://purl.uniprot.org/citations/33783314http://purl.org/dc/terms/identifier"doi:10.1080/15548627.2021.1896157"xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Chang H.C."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Chang H.C."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Tan C.T."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Tan C.T."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Wu Y.J."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Wu Y.J."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Yu V.C."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Yu V.C."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Tao R.N."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Tao R.N."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Bay B.H."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/author"Bay B.H."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/name"Autophagy"xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/name"Autophagy"xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/pages"3725-3739"xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/pages"3725-3739"xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/title"The BAX-binding protein MOAP1 associates with LC3 and promotes closure of the phagophore."xsd:string
http://purl.uniprot.org/citations/33783314http://purl.uniprot.org/core/title"The BAX-binding protein MOAP1 associates with LC3 and promotes closure of the phagophore."xsd:string
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