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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-θ), which physically associates with the regulatory regions of inducible immune response genes in human T cells. Chromatin-anchored PKC-θ forms an active nuclear complex by interacting with RNA polymerase II, the histone kinase MSK-1, and the adaptor molecule 14-3-3ζ. ChIP-on-chip reveals that PKC-θ 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-θ not only in normal T cell function, but also in circumstances of its ectopic expression in cancer.

Original publication

DOI

10.1016/j.molcel.2011.02.030

Type

Journal article

Journal

Mol Cell

Publication Date

18/03/2011

Volume

41

Pages

704 - 719

Keywords

Cell Line, Tumor, Cell Nucleus, Chromatin, Gene Expression Regulation, Humans, Interleukin-2, Isoenzymes, Jurkat Cells, MicroRNAs, Promoter Regions, Genetic, Protein Kinase C, Protein Kinase C-theta, RNA Polymerase II, Ribosomal Protein S6 Kinases, 90-kDa, T-Lymphocytes, Transcription, Genetic