| First Author | Wu JL | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 12526 | PubMed ID | 27555448 |
| Mgi Jnum | J:241619 | Mgi Id | MGI:5903188 |
| Doi | 10.1038/ncomms12526 | Citation | Wu JL, et al. (2016) Temporal regulation of Lsp1 O-GlcNAcylation and phosphorylation during apoptosis of activated B cells. Nat Commun 7:12526 |
| abstractText | 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-beta1, 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. |
