Temporal regulation of Lsp1 O-GlcNAcylation and phosphorylation during apoptosis of activated B cells

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Title:	Temporal regulation of Lsp1 O-GlcNAcylation and phosphorylation during apoptosis of activated B cells
Authors:	吳忻怡;Wu, Jung-Lin;Wu, Hsin-Yi;Tsai, Dong-Yan;Chiang, Ming-Feng;Chen, Yi-Ju;Gao, Shijay;Lin, Chun-Cheng;Lin, Chun-Hung;Khoo, Kay-Hooi;Chen, Yu-Ju;Lin, Kuo-I.
Contributors:	總教學中心通識教育中心
Keywords:	38/109;42/89;631/250/1619/40/1774;631/45/612/1231;631/45/612/1246;96/106;96/31;96/95;Acetylglucosamine - metabolism;Animals;Apoptosis;Apoptosis - drug effects;Apoptosis - immunology;B-Lymphocytes - cytology;B-Lymphocytes - immunology;B-Lymphocytes - metabolism;beta-N-Acetylhexosaminidases - antagonists & inhibitors;beta-N-Acetylhexosaminidases - metabolism;Calcium-Binding Proteins - chemistry;Calcium-Binding Proteins - metabolism;Cells;Enzyme Inhibitors - pharmacology;Glycosylation;Humanities and Social Sciences;Kinases;Lymphocyte Activation - drug effects;Lymphocytes;Mice;Mice, Inbred C57BL;multidisciplinary;Phosphorylation;Protein Kinase C beta - metabolism;Proteins;Pyrans - pharmacology;Science;Science (multidisciplinary);Signal Transduction;Thiazoles - pharmacology
Date:	2016-08-24
Issue Date:	2026-04-23 12:55:40 (UTC+8)
Publisher:	Nature Publishing Group;London: Springer Science and Business Media LLC
Abstract:	摘要： AbstractCrosslinking of B-cell receptor (BCR) sets off an apoptosis programme, but the underlying pathways remain obscure. Here we decipher the molecular mechanisms bridging B-cell activation and apoptosis mediated by post-translational modification (PTM). We find that O-GlcNAcase inhibition enhances B-cell activation and apoptosis induced by BCR crosslinking. This proteome-scale analysis of the functional interplay between protein O-GlcNAcylation and phosphorylation in stimulated mouse primary B cells identifies 313 O-GlcNAcylation-dependent phosphosites on 224 phosphoproteins. Among these phosphoproteins, temporal regulation of the O-GlcNAcylation and phosphorylation of lymphocyte-specific protein-1 (Lsp1) is a key switch that triggers apoptosis in activated B cells. O-GlcNAcylation at S209 of Lsp1 is a prerequisite for the recruitment of its kinase, PKC-β1, to induce S243 phosphorylation, leading to ERK activation and downregulation of BCL-2 and BCL-xL. Thus, we demonstrate the critical PTM interplay of Lsp1 that transmits signals for initiating apoptosis after BCR ligation. 其他題名： Nat Commun 出版者： London: Springer Science and Business Media LLC 出版日期： 2016-08-24 出處： Nature Communications, 2016-08, Vol.7 (1), p.12526--11, Article 12526 資源來源： Springer Nature Open Access Journals 版權： The Author(s) 2016 版權： Copyright Nature Publishing Group Aug 2016 版權： Copyright © 2016, The Author(s) 2016 The Author(s) 識別號： ISSN: 2041-1723 識別號： EISSN: 2041-1723 識別號： DOI: 10.1038/ncomms12526 識別號： PMID: 27555448
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