Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes

Maria N. Navarro, Jurgen Goebel, Carmen Feijoo-Carnero, Nick Morrice, Doreen A. Cantrell (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    65 Citations (Scopus)

    Abstract

    Here we report an unbiased analysis of the cytotoxic T lymphocyte (CTL) serine-threonine phosphoproteome by high-resolution mass spectrometry. We identified approximately 2,000 phosphorylations in CTLs, of which approximately 450 were controlled by T cell antigen receptor (TCR) signaling. A significantly overrepresented group of molecules identified included transcription activators, corepressors and chromatin regulators. A focus on chromatin regulators showed that CTLs had high expression of the histone deacetylase HDAC7 but continually phosphorylated and exported this transcriptional repressor from the nucleus. Dephosphorylation of HDAC7 resulted in its accumulation in the nucleus and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. Screening of the CTL phosphoproteome has thus identified intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators and determine the CTL functional program.

    Original languageEnglish
    Pages (from-to)352-361
    Number of pages11
    JournalNature Immunology
    Volume12
    Issue number4
    DOIs
    Publication statusPublished - Apr 2011

    Keywords

    • Nuclear export
    • Phosphatidylinositol 3-kinases physiology
    • Transcription factor
    • Enzymatic activity
    • Phosphorylation
    • Kinase
    • Activation
    • Expression
    • Apoptosis
    • Cells

    Cite this

    @article{67ced0841a0146428c8d5ad88787b02a,
    title = "Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes",
    abstract = "Here we report an unbiased analysis of the cytotoxic T lymphocyte (CTL) serine-threonine phosphoproteome by high-resolution mass spectrometry. We identified approximately 2,000 phosphorylations in CTLs, of which approximately 450 were controlled by T cell antigen receptor (TCR) signaling. A significantly overrepresented group of molecules identified included transcription activators, corepressors and chromatin regulators. A focus on chromatin regulators showed that CTLs had high expression of the histone deacetylase HDAC7 but continually phosphorylated and exported this transcriptional repressor from the nucleus. Dephosphorylation of HDAC7 resulted in its accumulation in the nucleus and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. Screening of the CTL phosphoproteome has thus identified intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators and determine the CTL functional program.",
    keywords = "Nuclear export, Phosphatidylinositol 3-kinases physiology, Transcription factor, Enzymatic activity, Phosphorylation, Kinase, Activation, Expression, Apoptosis, Cells",
    author = "Navarro, {Maria N.} and Jurgen Goebel and Carmen Feijoo-Carnero and Nick Morrice and Cantrell, {Doreen A.}",
    year = "2011",
    month = "4",
    doi = "10.1038/ni.2008",
    language = "English",
    volume = "12",
    pages = "352--361",
    journal = "Nature Immunology",
    issn = "1529-2908",
    publisher = "Nature Publishing Group",
    number = "4",

    }

    Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes. / Navarro, Maria N.; Goebel, Jurgen; Feijoo-Carnero, Carmen; Morrice, Nick; Cantrell, Doreen A. (Lead / Corresponding author).

    In: Nature Immunology, Vol. 12, No. 4, 04.2011, p. 352-361.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes

    AU - Navarro, Maria N.

    AU - Goebel, Jurgen

    AU - Feijoo-Carnero, Carmen

    AU - Morrice, Nick

    AU - Cantrell, Doreen A.

    PY - 2011/4

    Y1 - 2011/4

    N2 - Here we report an unbiased analysis of the cytotoxic T lymphocyte (CTL) serine-threonine phosphoproteome by high-resolution mass spectrometry. We identified approximately 2,000 phosphorylations in CTLs, of which approximately 450 were controlled by T cell antigen receptor (TCR) signaling. A significantly overrepresented group of molecules identified included transcription activators, corepressors and chromatin regulators. A focus on chromatin regulators showed that CTLs had high expression of the histone deacetylase HDAC7 but continually phosphorylated and exported this transcriptional repressor from the nucleus. Dephosphorylation of HDAC7 resulted in its accumulation in the nucleus and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. Screening of the CTL phosphoproteome has thus identified intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators and determine the CTL functional program.

    AB - Here we report an unbiased analysis of the cytotoxic T lymphocyte (CTL) serine-threonine phosphoproteome by high-resolution mass spectrometry. We identified approximately 2,000 phosphorylations in CTLs, of which approximately 450 were controlled by T cell antigen receptor (TCR) signaling. A significantly overrepresented group of molecules identified included transcription activators, corepressors and chromatin regulators. A focus on chromatin regulators showed that CTLs had high expression of the histone deacetylase HDAC7 but continually phosphorylated and exported this transcriptional repressor from the nucleus. Dephosphorylation of HDAC7 resulted in its accumulation in the nucleus and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. Screening of the CTL phosphoproteome has thus identified intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators and determine the CTL functional program.

    KW - Nuclear export

    KW - Phosphatidylinositol 3-kinases physiology

    KW - Transcription factor

    KW - Enzymatic activity

    KW - Phosphorylation

    KW - Kinase

    KW - Activation

    KW - Expression

    KW - Apoptosis

    KW - Cells

    UR - http://www.scopus.com/inward/record.url?scp=79952962027&partnerID=8YFLogxK

    U2 - 10.1038/ni.2008

    DO - 10.1038/ni.2008

    M3 - Article

    VL - 12

    SP - 352

    EP - 361

    JO - Nature Immunology

    JF - Nature Immunology

    SN - 1529-2908

    IS - 4

    ER -