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

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 Nature Communications  
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
more » ... 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-b1, 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.
doi:10.1038/ncomms12526 pmid:27555448 pmcid:PMC4999498 fatcat:jzc222cbxnaw3ibia4jpkudc5y