Please use this identifier to cite or link to this item:
https://doi.org/10.1080/15548627.2021.1896157
DC Field | Value | |
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dc.title | The BAX-binding protein MOAP1 associates with LC3 and promotes closure of the phagophore | |
dc.contributor.author | Hao-Chun Chang | |
dc.contributor.author | Ran N. Tao | |
dc.contributor.author | Chong Teik Tan | |
dc.contributor.author | Ya jun Wu | |
dc.contributor.author | Boon Huat Bay | |
dc.contributor.author | Victor C. Yu | |
dc.date.accessioned | 2021-12-17T01:14:54Z | |
dc.date.available | 2021-12-17T01:14:54Z | |
dc.date.issued | 2021-03-30 | |
dc.identifier.citation | Hao-Chun Chang, Ran N. Tao, Chong Teik Tan, Ya jun Wu, Boon Huat Bay, Victor C. Yu (2021-03-30). The BAX-binding protein MOAP1 associates with LC3 and promotes closure of the phagophore. Autophagy 17 (11) : 3725-3739. ScholarBank@NUS Repository. https://doi.org/10.1080/15548627.2021.1896157 | |
dc.identifier.issn | 1554-8627 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/210948 | |
dc.description.abstract | 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. | |
dc.publisher | Taylor & Francis | |
dc.source | Taylor & Francis | |
dc.subject | Autophagosome formation | |
dc.subject | autophagy | |
dc.subject | cell death | |
dc.subject | LC3-binding protein | |
dc.subject | LIR motif | |
dc.subject | nutrient deprivation | |
dc.type | Article | |
dc.contributor.department | DEPT OF PHARMACY | |
dc.contributor.department | DEPT OF ANATOMY | |
dc.description.doi | 10.1080/15548627.2021.1896157 | |
dc.description.sourcetitle | Autophagy | |
dc.description.volume | 17 | |
dc.description.issue | 11 | |
dc.description.page | 3725-3739 | |
Appears in Collections: | Elements Staff Publications |
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