Evaluation of Tankyrase Inhibition in Whole Cells
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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.
Affiliation(s): (2) Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
Book Title: Telomerase Inhibition: Strategies and Protocols
Series: Methods in Molecular Biology | Volume: 405 | Pub. Date: Nov-29-2007 | Page Range: 133-146 | DOI: 10.1007/978-1-60327-070-0_11
Subject: Cell Biology
Key Words: Telemere - telomerase - tankyrase 1 - PARP - TRF1 - electroporation - immunofluo-rescence microscopy - drug screening
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