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New PARP targets for cancer therapy

Nature Reviews Cancer volume 14, pages 502–509 (2014)Cite this article

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Abstract

Poly(ADP-ribose) polymerases (PARPs) modify target proteins post-translationally with poly(ADP-ribose) (PAR) or mono(ADP-ribose) (MAR) using NAD+ as substrate. The best-studied PARPs generate PAR modifications and include PARP1 and the tankyrase PARP5A, both of which are targets for cancer therapy with inhibitors in either clinical trials or preclinical development. There are 15 additional PARPs, most of which modify proteins with MAR, and their biology is less well understood. Recent data identify potentially cancer-relevant functions for these PARPs, which indicates that we need to understand more about these PARPs to effectively target them.

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Figure 1: Sequence and structural elements of the poly(ADP-ribose) polymerase (PARP) catalytic domain.
Figure 2: Two forms of ADP-ribose modifications.
Figure 3: Cellular functions of the poly(ADP-ribose) polymerase (PARP) family.

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Acknowledgements

The authors thank F. Solomon, M. Vander Heiden, J. Pascal and F. Bock for their helpful comments and discussion about the manuscript. This work is supported by a grant to P.C. from the US National Institutes of Health (ROI GM087465) and was partially supported by Cancer Center Support (core; grant P30-CA14051).

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  1. Koch Institute for Integrative Cancer Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Sejal Vyas & Paul Chang

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  1. Sejal Vyas
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Correspondence to Paul Chang.

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Vyas, S., Chang, P. New PARP targets for cancer therapy. Nat Rev Cancer 14, 502–509 (2014). https://doi.org/10.1038/nrc3748

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