GCN5 regulates the activation of PI3K/Akt survival pathway in B cells exposed to oxidative stress via controlling gene expressions of Syk and Btk
Copyright policy )GCN5 regulates the activation of PI3K/Akt survival pathway in B cells exposed to oxidative stress via controlling gene expressions of Syk and Btk
Histone acetyltransferase(s) (HATs) are involved in the acetylation of core histones, which is an important event for transcription regulation through alterations in the chromatin structure in eukaryotes. General control non-depressible 5 (GCN5) was first identified as a global coactivator and transcription-related HAT. Here we report that GCN5 regulates the activation of phosphatidylinositol 3-kinase (PI3K)/acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) survival pathway in B cells exposed to oxidative stress via controlling gene expressions of spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk). The GCN5-deficiency remarkably caused apoptotic cell death by treatment with exogenous hydrogen peroxide (H(2)O(2)) in chicken DT40 cells. In GCN5-deficient DT40 cells, gene expressions of Syk and Btk, which are involved in activation of PI3K/Akt survival pathway in DT40 cells exposed to exogenous H(2)O(2), were remarkably decreased compared with those in wild type DT40 cells. In addition, phosphorylation of Akt in H(2)O(2)-treated GCN5-deficient cells was remarkably suppressed as compared to that of DT40. Chromatin immunoprecipitation assay revealed that GCN5 binds to proximal 5'-upstream regions of Syk and Btk genes in vivo. These results suggest that GCN5 takes part in transcriptional regulations of the Syk and Btk genes, and plays a key role in epigenetic regulation of PI3K/Akt survival pathway in B cells exposed to reactive oxygen species such as H(2)O(2).
- University of Tokyo Japan
- University of Miyazaki Japan
- Kawasaki Medical School Japan
- Miyazaki Welfare Medical College Japan
B-Lymphocytes, Chromatin Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Apoptosis, Hydrogen Peroxide, Protein-Tyrosine Kinases, Gene Expression Regulation, Enzymologic, Cell Line, Enzyme Activation, Oxidative Stress, Phosphatidylinositol 3-Kinases, Mutation, Agammaglobulinaemia Tyrosine Kinase, Animals, Syk Kinase, p300-CBP Transcription Factors, Chickens, Proto-Oncogene Proteins c-akt
B-Lymphocytes, Chromatin Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Apoptosis, Hydrogen Peroxide, Protein-Tyrosine Kinases, Gene Expression Regulation, Enzymologic, Cell Line, Enzyme Activation, Oxidative Stress, Phosphatidylinositol 3-Kinases, Mutation, Agammaglobulinaemia Tyrosine Kinase, Animals, Syk Kinase, p300-CBP Transcription Factors, Chickens, Proto-Oncogene Proteins c-akt
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