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TIPs: Tankyrase Interacting Proteins

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PARP Inhibitors for Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D,volume 83))

Abstract

Tankyrase 1 and tankyrase 2 are “card carrying” members of the poly(ADP-ribose) polymerase (PARP) family of enzymes. PARPs use NAD + as a substrate to generate ADP-ribose polymers on protein acceptors. For over thirty years PARP-1 reigned supreme as the original and only known protein with this unusual enzymatic activity. Then, beginning in 1998 new functionally distinct PARPs, tankyrase 1 among them, were reported. Tankyrase 1 was found in a two-hybrid screen with the telomere-specific DNA binding protein TRF1. Subsequently in 2000, a closely related homolog tankyrase 2 was found in a two-hybrid screen with the insulin-responsive amino peptidase (IRAP). Tankyrases have a catalytic PARP domain in common with PARP-1, but are distinguished by a large ankyrin repeat domain that serves as a platform for numerous, diverse protein binding partners, resulting in a remarkable range of biological activities involved in telomere function, inherited disease, and cancer. With the recent discovery of potent tankyrase-specific small molecule inhibitors, understanding the diverse functions of tankyrases has become more than just a fascinating cell biological puzzle. Elucidation of tankyrase function will pave the way for future therapeutic strategies, while at the same time provide insights into potential deleterious side effects.

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Acknowledgements

We thank Amit Bhardwaj and Ekta Tripathi for comments on the manuscript and Sam Meier and Abe Ratnofsky for figure preparation. The work on tankyrases in the Smith lab is supported by NIH NCI grant CA095099.

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  1. Department of Pathology, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 10016, New York, NY, USA

    Susan Smith

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  1. Northern Institute for Cancer Research and Newcastle University Institute for Ageing Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom

    Nicola J. Curtin

  2. CRUK-MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom

    Ricky A. Sharma

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Smith, S. (2015). TIPs: Tankyrase Interacting Proteins. In: Curtin, N., Sharma, R. (eds) PARP Inhibitors for Cancer Therapy. Cancer Drug Discovery and Development, vol 83. Humana Press, Cham. https://doi.org/10.1007/978-3-319-14151-0_4

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