Summary
The telomeric poly(ADP-ribose) polymerase (PARP), tankyrase 1, modulates the impact of telomerase inhibition on human cancer cells. Thus, overexpression of tankyrase 1 in telomerase-positive cancer cells confers resistance to telomerase inhibitors, such as MST-312, whereas pharmacological inhibition of tankyrase 1 enhances telomere shortening by MST-312. These facts indicate that tankyrase 1 could be a target for telomere-directed molecular cancer therapy. Here, the authors describe a convenient method to monitor the telomeric function of tankyrase 1. This protocol takes much less time than the telomere Southern blot analysis and can be utilized as a rapid screening system for tankyrase 1 inhibitors that are effective in intact cells. For direct monitoring of tankyrase 1 PARP activity, a protocol for the in vitro enzyme assay is also described.
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Acknowledgments
We thank Yukiko Muramatsu and Michiko Sakamoto for technical assistance and Susan Smith for scientific advice. This work was funded in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and grants from the Kato Memorial Bioscience Foundation and the Vehicle Racing Commemorative Foundation, Japan.
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Ohishi, T., Tsuruo, T., Seimiya, H. (2007). Evaluation of Tankyrase Inhibition in Whole Cells. In: Andrews, L.G., Tollefsbol, T.O. (eds) Telomerase Inhibition. Methods in Molecular Biology™, vol 405. Humana Press. https://doi.org/10.1007/978-1-60327-070-0_11
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DOI: https://doi.org/10.1007/978-1-60327-070-0_11
Publisher Name: Humana Press
Print ISBN: 978-1-58829-683-2
Online ISBN: 978-1-60327-070-0
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