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

  title={Temporal regulation of Lsp1 O-GlcNAcylation and phosphorylation during apoptosis of activated B cells},
  author={Jung-Lin Wu and Hsin‐Yi Wu and Dong-Yan Tsai and Ming-Feng Chiang and Yi‐Ju Chen and Shijay Gao and Chun‐Cheng Lin and Chun-Hung Lin and Kay-Hooi Khoo and Yu‐Ju Chen and Kuo-I Lin},
  journal={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… 
Increased O-GlcNAcylation of c-Myc Promotes Pre-B Cell Proliferation
It is demonstrated that changes in cellular O-GlcNAcylation levels significantly affected the growth of pre-B cells, which rapidly proliferate to allow expansion of functional clones that express successfully rearranged heavy chains at the pro-B stage during early B cell development.
O-GlcNAcylation is required for B cell homeostasis and antibody responses
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LPS induces GFAT2 expression to promote O-GlcNAcylation and attenuate inflammation in macrophages
GFAT2 should be considered as a new TLR4-inducible gene involved in regulation of protein O-GlcNAcylation, that permits to limit exacerbated inflammation upon macrophage activation.
O-GlcNAcylation and Its Role in Cancer-Associated Inflammation
The current understanding of the influence of protein O-GlcNAcylation on cancer-associated inflammation and the mechanisms whereby O- GlcNAc-mediated inflammation regulates tumor progression are summarized to provide a theoretical basis for further development of anti-cancer therapies.
Lipopolysaccharide Induces GFAT2 Expression to Promote O-Linked β-N-Acetylglucosaminylation and Attenuate Inflammation in Macrophages
GFAT2 should be considered a new LPS-inducible gene involved in regulation of protein O-GlcNAcylation, which permits limited exacerbation of inflammation upon macrophage activation, and may restrain inflammatory processes induced by LPS.
O-GlcNAcylation and its role in the immune system
O-GlcNAcylation promotes the development, proliferation, and activation of T and B cells, and regulates inflammatory and antiviral responses of macrophages, but inhibits the activity of nature killer cells.
The role of O‐GlcNAcylation in immunity against infections
Whether targeting of O‐GlcNAcylation could hold promise as a therapeutic approach to modulate immune responses to infections is explored.


Microfilament assembly is involved in B-cell apoptosis.
It is demonstrated that crosslinking of the human BCR with anti-IgM antibodies results in the rapid assembly of actin, and results suggest that the microfilament system is actively involved in delivering signals for apoptosis.
Requirement for O‐linked N‐acetylglucosaminyltransferase in lymphocytes activation
It is demonstrated that OGT is a central factor for T‐ and B‐lymphocytes activation and its modification prominently increased shortly after activation of lymphoid cells and it might be required for nuclear translocation of the transcription factors NFκB and NFAT.
Involvement of Histone Demethylase LSD1 in Blimp-1-Mediated Gene Repression during Plasma Cell Differentiation
It is reported that a proline-rich domain in Blimp-1 directly interacts with LSD1, a histone lysine demethylase, and that LSD1 binding correlates with histone modifications of accessible chromatin.
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A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo.
Thiamet-G will find wide use in probing the functional role of O-GlcNAc in vertebrate brain, and it may also offer a route to blocking pathological hyperphosphorylation of tau in AD.
Lymphocyte activation induces rapid changes in nuclear and cytoplasmic glycoproteins.
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    Proceedings of the National Academy of Sciences of the United States of America
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Results indicate that the apparent levels of O-GlcNAc on many nuclear proteins increases rapidly after lymphocyte activation, returning to control levels after a few hours, and suggest that O- GloverNAc modification may play an important role in the early stages of T-lymphocyte activation.
Induction of apoptosis in plasma cells by B lymphocyte-induced maturation protein-1 knockdown.
It is found that knockdown of Blimp-1 expression by lentiviral vector-delivered short hairpin RNA causes apoptosis in multiple myeloma cell lines and plasmacytoma cells, indicating that continued expression of Blimp-1 is required for cell survival.
Leukocyte-specific protein 1 targets the ERK/MAP kinase scaffold protein KSR and MEK1 and ERK2 to the actin cytoskeleton
The data show that LSP1 is a cytoskeletal targeting protein for the ERK/MAP kinase pathway and support a model in which MEK1 and ERK2 are organized in a cytOSkeletal signaling complex together with KSR, PKCβI and L SP1 and are activated by anti-IgM in a PKC βI-dependent manner.