title: Temporal regulation of Lsp1 O-GlcNAcylation and phosphorylation during apoptosis of activated B cells.
abstract: Crosslinking 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.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan.|Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Jung-Lin
authors.identifier: 0000-0003-1054-9016
authors.initials: JL
authors.lastname: Wu
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Wu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.|Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Tsai
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Chiang
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Shijay
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Kuo-I
authors.initials: KI
authors.lastname: Lin
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006031:Glycosylation; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins; D010766:Phosphorylation; D064546:Protein Kinase C beta / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004791:Enzyme Inhibitors; C057701:Lsp1 protein, mouse; D008840:Microfilament Proteins; D011714:Pyrans; D013844:Thiazoles; C572247:thiamet G; D064546:Protein Kinase C beta; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine