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D-type Cyclins and Cancer pp 61–90Cite as

D-Type Cyclins and Gene Transcription

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Part of the book series: Current Cancer Research ((CUCR))

Abstract

D-type cyclins contribute the regulatory subunits to the holoenzymes that phosphorylate distinct substrates and regulate diverse biological processes, including cellular proliferation and differentiation. A growing body of evidence has demonstrated that the D-type cyclins are located in distinct subcellular pools with distinct functions. These subcellular locations include the cell membrane, the cytoplasm, the nuclear lamina, the nucleus, and DNA binding sites. The distribution of D-type cyclins in each one of these compartments is regulated by distinct signaling pathways and contributes to a vast array of biological processes. Importantly, D-type cyclins can also conduct transcriptional functions. Initially shown to regulate the activity of transcription factors in gene reporter assays, subsequent studies have shown that D-type cyclins can affect gene expression through the regulation of coactivators, the modulation of transcription factor binding in the context of chromatin, and their ability to serve as molecular scaffolds that facilitate the interactions between chromatin-modifying enzymes (histone and DNA methylases [Suv39, HP1α, G9a, DNMT1, PRMT1], histone acetylases [SRC1, p300, P/CAF], and histone deacetylases [HDAC1,3]). Genome-wide studies have shown that cyclin D1 associates with the regulatory regions of more than 2840 genes. The importance of the transcriptional functions of D-type cyclins has been demonstrated in vivo, as hormone signaling in prostate and mammary gland tissues is critically dependent upon the presence of cyclin D1. Furthermore, it is the cyclin D1-regulated gene expression signature, not the abundance of the protein, which strongly predicts poor outcome in prostate cancer. Together, these findings are consistent with the evolving realization that the D-type cyclins play an important biological role in governing gene transcription.

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Acknowledgments

This work was supported in part by 1R01CA137494 R01 CA 132115-05A1 (R.G.P.). The Sidney Kimmel Cancer Center was supported by the NIH Cancer Center Core Grant P30CA56036 (R.G.P). This project is funded in part from the Breast Cancer Research Foundation (R.G.P), Dr. Ralph and Marian C. Falk Medical Research Trust (R.G.P), and a grant from Pennsylvania Department of Health (R.G.P.). The department specifically disclaims responsibility for analyses, interpretations, or conclusions.

We sincerely apologize to any authors whose contributions to this field have not been fully described due to the limitations of size for this chapter.

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Author notes

  1. Gabriele Di Sante and Mathew C. Casimiro contributed equally to this work.

Authors and Affiliations

  1. Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, Pennsylvania Biotechnology Center, 100 East Lancaster Avenue, Suite, 222, Wynnewood, PA, 19096, USA

    Gabriele Di Sante, Mathew C. Casimiro & Richard G. Pestell

  2. Department of Cancer Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA, 19107, USA

    Zhiping Li & Adam Ertel

  3. VIB center for Structural Biology (CSB), Brussels, Belgium

    Peter Tompa

  4. Structural Biology Brussels (SBB), Vrije Universiteit Brussel (VUB), Brussels, Belgium

    Peter Tompa

  5. Institute of Enzymology, Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Budapest, Hungary

    Peter Tompa

  6. Lee Kong Chian School of Medicine, Nanyang Technological University, 639798, Singapore, Singapore

    Richard G. Pestell

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  1. Gabriele Di Sante
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  1. Tufts University School of Medicine, Boston, Massachusetts, USA

    Philip W. Hinds

  2. University of Talca Medical School, Talca, Chile

    Nelson E. Brown

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Di Sante, G., Casimiro, M.C., Li, Z., Ertel, A., Tompa, P., Pestell, R.G. (2018). D-Type Cyclins and Gene Transcription. In: Hinds, P., Brown, N. (eds) D-type Cyclins and Cancer. Current Cancer Research. Springer, Cham. https://doi.org/10.1007/978-3-319-64451-6_3

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  • DOI: https://doi.org/10.1007/978-3-319-64451-6_3

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  • Online ISBN: 978-3-319-64451-6

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