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

Elissa Sutcliffe; Karen Bunting; Yi Qing He; Jasmine Li; Chansavath Phetsouphanh; nabila seddiki; Anjum Zafar; Elizabeth Hindmarsh; Christopher Parish; Anthony Kelleher; Russell L. Mcinness; Taya Toshiki; Peter Milburn; Sudha Rao

doi:10.1016/j.molcel.2011.02.030

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

Elissa Sutcliffe, Karen Bunting, Yi Qing He, Jasmine Li, Chansavath Phetsouphanh, nabila seddiki, Anjum Zafar, Elizabeth Hindmarsh, Christopher Parish, Anthony Kelleher, Russell L. Mcinness, Taya Toshiki, Peter Milburn, Sudha Rao

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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

Original language	English
Pages (from-to)	704-719
Number of pages	16
Journal	Molecular Cell
Volume	41
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2011.02.030
Publication status	Published - 2011

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Sutcliffe, E., Bunting, K., He, Y. Q., Li, J., Phetsouphanh, C., seddiki, N., Zafar, A., Hindmarsh, E., Parish, C., Kelleher, A., Mcinness, R. L., Toshiki, 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, 41(6), 704-719. https://doi.org/10.1016/j.molcel.2011.02.030

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

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",

author = "Elissa Sutcliffe and Karen Bunting and He, {Yi Qing} and Jasmine Li and Chansavath Phetsouphanh and nabila seddiki and Anjum Zafar and Elizabeth Hindmarsh and Christopher Parish and Anthony Kelleher and Mcinness, {Russell L.} and Taya Toshiki and Peter Milburn and Sudha Rao",

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doi = "10.1016/j.molcel.2011.02.030",

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Sutcliffe, E, Bunting, K, He, YQ, Li, J, Phetsouphanh, C, seddiki, N, Zafar, A, Hindmarsh, E, Parish, C, Kelleher, A, Mcinness, RL, Toshiki, 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

TY - JOUR

T1 - Chromatin associated protein kinase C- regulates an inducible gene expression program and microRNAs in human T lymphocytes

AU - Sutcliffe, Elissa

AU - Bunting, Karen

AU - He, Yi Qing

AU - Li, Jasmine

AU - Phetsouphanh, Chansavath

AU - seddiki, nabila

AU - Zafar, Anjum

AU - Hindmarsh, Elizabeth

AU - Parish, Christopher

AU - Kelleher, Anthony

AU - Mcinness, Russell L.

AU - Toshiki, Taya

AU - Milburn, Peter

AU - Rao, Sudha

PY - 2011

Y1 - 2011

N2 - 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

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

U2 - 10.1016/j.molcel.2011.02.030

DO - 10.1016/j.molcel.2011.02.030

M3 - Article

SN - 1097-2765

VL - 41

SP - 704

EP - 719

JO - Molecular Cell

JF - Molecular Cell

IS - 6

ER -

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

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