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

Author

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  • Jung-Lin Wu

    (Institute of Microbiology and Immunology, National Yang-Ming University
    Genomics Research Center, Academia Sinica)

  • Hsin-Yi Wu

    (Institute of Chemistry, Academia Sinica)

  • Dong-Yan Tsai

    (Genomics Research Center, Academia Sinica
    Institute of Biochemistry and Molecular Biology, National Yang-Ming University)

  • Ming-Feng Chiang

    (Genomics Research Center, Academia Sinica)

  • Yi-Ju Chen

    (Institute of Chemistry, Academia Sinica)

  • Shijay Gao

    (Institute of Biological Chemistry, Academia Sinica)

  • Chun-Cheng Lin

    (National Tsing Hua University)

  • Chun-Hung Lin

    (Institute of Biological Chemistry, Academia Sinica)

  • Kay-Hooi Khoo

    (Institute of Biological Chemistry, Academia Sinica)

  • Yu-Ju Chen

    (Institute of Chemistry, Academia Sinica)

  • Kuo-I. Lin

    (Genomics Research Center, Academia Sinica)

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.

Suggested Citation

  • Jung-Lin Wu & Hsin-Yi Wu & Dong-Yan Tsai & Ming-Feng Chiang & Yi-Ju Chen & Shijay Gao & Chun-Cheng Lin & Chun-Hung Lin & Kay-Hooi Khoo & Yu-Ju Chen & Kuo-I. Lin, 2016. "Temporal regulation of Lsp1 O-GlcNAcylation and phosphorylation during apoptosis of activated B cells," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12526
    DOI: 10.1038/ncomms12526
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