Chromatin associated protein kinase C- regulates an inducible gene expression program and microRNAs in human T lymphocytes

Elissa Sutcliffe, Karen Bunting, Y He, J Li, Anjum Zafar, E Hindmarsh, Christopher Parish, R Mcinness, Tauhid Taya, Peter Milburn, Sudha Rao

    Research output: Contribution to journalArticle

    43 Citations (Scopus)

    Abstract

    Studies in yeast demonstrate that signaling kinases have a surprisingly active role in the nucleus, where they tether to chromatin and modulate gene expression programs. Despite these seminal studies, the nuclear mechanism of how signaling kinases control transcription of mammalian genes is in its infancy. Here, we provide evidence for a hitherto unknown function of protein kinase C-theta (PKC-theta), which physically associates with the regulatory regions of inducible immune response genes in human T cells. Chromatin-anchored PKC-theta forms an active nuclear complex by interacting with RNA polymerase II, the histone kinase MSK-1, and the adaptor molecule 14-3-3 zeta. ChIP-on-chip reveals that PKC-theta binds to promoters and transcribed regions of genes, as well as to microRNA promoters that are crucial for cytokine regulation. Our results provide a molecular explanation for the role of PKC-theta not only in normal T cell function, but also in circumstances of its ectopic expression in cancer
    Original languageEnglish
    Pages (from-to)704-719
    Number of pages16
    JournalMolecular Cell
    Volume41
    Issue number6
    DOIs
    Publication statusPublished - 2011

    Fingerprint

    MicroRNAs
    Protein Kinase C
    Chromatin
    T-Lymphocytes
    Gene Expression
    Phosphotransferases
    Protamine Kinase
    Genes
    RNA Polymerase II
    Nucleic Acid Regulatory Sequences
    Genetic Promoter Regions
    Yeasts
    Cytokines
    Neoplasms

    Cite this

    Sutcliffe, Elissa ; Bunting, Karen ; He, Y ; Li, J ; Zafar, Anjum ; Hindmarsh, E ; Parish, Christopher ; Mcinness, R ; Taya, Tauhid ; Milburn, Peter ; Rao, Sudha. / Chromatin associated protein kinase C- regulates an inducible gene expression program and microRNAs in human T lymphocytes. In: Molecular Cell. 2011 ; Vol. 41, No. 6. pp. 704-719.
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    abstract = "Studies in yeast demonstrate that signaling kinases have a surprisingly active role in the nucleus, where they tether to chromatin and modulate gene expression programs. Despite these seminal studies, the nuclear mechanism of how signaling kinases control transcription of mammalian genes is in its infancy. Here, we provide evidence for a hitherto unknown function of protein kinase C-theta (PKC-theta), which physically associates with the regulatory regions of inducible immune response genes in human T cells. Chromatin-anchored PKC-theta forms an active nuclear complex by interacting with RNA polymerase II, the histone kinase MSK-1, and the adaptor molecule 14-3-3 zeta. ChIP-on-chip reveals that PKC-theta binds to promoters and transcribed regions of genes, as well as to microRNA promoters that are crucial for cytokine regulation. Our results provide a molecular explanation for the role of PKC-theta not only in normal T cell function, but also in circumstances of its ectopic expression in cancer",
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    Sutcliffe, E, Bunting, K, He, Y, Li, J, Zafar, A, Hindmarsh, E, Parish, C, Mcinness, R, Taya, T, Milburn, P & Rao, S 2011, 'Chromatin associated protein kinase C- regulates an inducible gene expression program and microRNAs in human T lymphocytes', Molecular Cell, vol. 41, no. 6, pp. 704-719. https://doi.org/10.1016/j.molcel.2011.02.030

    Chromatin associated protein kinase C- regulates an inducible gene expression program and microRNAs in human T lymphocytes. / Sutcliffe, Elissa; Bunting, Karen; He, Y; Li, J; Zafar, Anjum; Hindmarsh, E; Parish, Christopher; Mcinness, R; Taya, Tauhid; Milburn, Peter; Rao, Sudha.

    In: Molecular Cell, Vol. 41, No. 6, 2011, p. 704-719.

    Research output: Contribution to journalArticle

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    AU - Hindmarsh, E

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    AU - Rao, Sudha

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    AB - Studies in yeast demonstrate that signaling kinases have a surprisingly active role in the nucleus, where they tether to chromatin and modulate gene expression programs. Despite these seminal studies, the nuclear mechanism of how signaling kinases control transcription of mammalian genes is in its infancy. Here, we provide evidence for a hitherto unknown function of protein kinase C-theta (PKC-theta), which physically associates with the regulatory regions of inducible immune response genes in human T cells. Chromatin-anchored PKC-theta forms an active nuclear complex by interacting with RNA polymerase II, the histone kinase MSK-1, and the adaptor molecule 14-3-3 zeta. ChIP-on-chip reveals that PKC-theta binds to promoters and transcribed regions of genes, as well as to microRNA promoters that are crucial for cytokine regulation. Our results provide a molecular explanation for the role of PKC-theta not only in normal T cell function, but also in circumstances of its ectopic expression in cancer

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