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Therapeutic Targets and Drugs III: Tankyrase 1, Telomere-Binding Proteins, and Inhibitors

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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

Telomere maintenance by telomerase enables cancer cells to proliferate indefinitely. Telomerase inhibitors resume the end replication problem and gradually shorten telomeres in telomerase-positive cancer cells. Critically shortened telomeres elicit a DNA damage response and induce senescence, apoptosis, or both. Accordingly, telomerase inhibition is one of the rational strategies for cancer therapy. Meanwhile, there are increasing numbers of telomere-binding proteins that maintain telomere integrity. Among them, tankyrase 1, a telomeric poly(ADP-ribose) polymerase, is one of the most druggable targets, whose enzymatic inhibition enhances the anticancer impact of telomerase inhibitors. Telomere capping is accomplished by sufficient lengths of double- and single-stranded telomeric DNA and their association with shelterin, which consists of TRF1, TRF2, TIN2, Rap1, TPP1, and POT1. Disruption of shelterin function leads to prompt telomere decapping, followed by DNA damage response and growth inhibition. In this chapter, we review telomere length regulation by tankyrase 1 and telomere protection by TRF2 and POT1, as potential target events for telomere-directed molecular cancer therapeutics.

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Authors and Affiliations

  1. Japanese Foundation for Cancer Research, Division of Molecular Biotherapy, Cancer Chemotherapy Center, 3-10-6 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Hiroyuki Seimiya

  2. Japanese Foundation for Cancer Research, Cancer Chemotherapy Center, Tokyo, Japan

    Takashi Tsuruo

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  1. Hiroyuki Seimiya
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  2. Takashi Tsuruo
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Editors and Affiliations

  1. Dept. Translational Cancer Research, Hiroshima University, 1-2-3 Kasumi, Hiroshima, Minami-Ku, 734-8551, Japan

    Keiko Hiyama

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Seimiya, H., Tsuruo, T. (2009). Therapeutic Targets and Drugs III: Tankyrase 1, Telomere-Binding Proteins, and Inhibitors. 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_12

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  • DOI: https://doi.org/10.1007/978-1-60327-879-9_12

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60327-306-0

  • Online ISBN: 978-1-60327-879-9

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