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 journalArticlepeer-review

    89 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

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