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Regulation of Telomerase Through Transcriptional and Posttranslational Mechanisms

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Telomeres and Telomerase in Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

The enzyme telomerase is associated with nearly 90% of human cancers. To better understand telomerase at the molecular level, a number of proteins involved in its regulation, either directly or indirectly, have been identified. This chapter aims to give a broad overview of both transcriptional and posttranslational telomerase-regulating proteins. Telomeraseistranscriptionally repressed and activatedbyproteins acting on the promoter region, suchas the Mad/Max heterodimer, c-Myc, p53, and Rb. Various kinases and ubiquitin ligases interact with telomerase, suggesting that phos-phorylation and ubiquitination play important roles in inhibiting and activating the enzyme. Also includedinthis chapter are proteins that regulate localizationof hTERT, assemblyofhTERT, hTR regulators, and telomere-bindingproteins that associate with telomerase. By gaining a better understanding of how telomerase is regulated, we can identify ways to block the enzyme in cancer cells or to activate the enzyme in normal cells as a means of modifying the cellular aging process.

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Authors and Affiliations

  1. Department of Human Genetics, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA, USA

    Amy N. Depcrynski & Patrick C. Sachs

  2. Department of Pathology and Massey Cancer Center, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA, USA

    Lynne W. Elmore

  3. Department of Human Genetics, Department of Pathology, Department of Pharmacology and Toxicology, Massey Cancer Center, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA, 23298-0662, USA

    Shawn E. Holt

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  1. Amy N. Depcrynski
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  2. Patrick C. Sachs
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  4. Shawn E. Holt
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  1. Dept. Translational Cancer Research, Hiroshima University, 1-2-3 Kasumi, Hiroshima, Minami-Ku, 734-8551, Japan

    Keiko Hiyama

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Depcrynski, A.N., Sachs, P.C., Elmore, L.W., Holt, S.E. (2009). Regulation of Telomerase Through Transcriptional and Posttranslational Mechanisms. In: Hiyama, K. (eds) Telomeres and Telomerase in Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-879-9_3

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