Discovery of the PARP Superfamily and Focus on the Lesser Exhibited But Not Lesser Talented Members

Poly(ADP-ribosyl)ation is a post-translational modification of proteins in which ADP-ribose units are sequentially transferred from the substrate NAD+ to acceptor proteins on glutamate, aspartate or lysine residues. The enzymes that catalyse this process are commonly called poly(ADP-ribose) polymerases or PARPs. In human, 17 proteins have been gathered in the PARP superfamily, based on their sequence homology with the catalytic domain of its founding member, PARP-1. In the first part of this chapter, we will recapitulate the history of the discovery of the PARP superfamily. Several excellent reviews have already presented biological processes involving PARP proteins, describing their involvement in DNA repair, transcription, post-transcriptional regulation, stress immunity and inflammation or (Feijs KL, Verheugd P, Luscher B (2013) Expanding functions of intracellular resident monoADP-ribosylation in cell physiology. FEBS J 280(15):3519–3529; Kleine H, Luscher B (2009) Learning how to read ADPribosylation. Cell 139(1):17–19; Gibson BA, Kraus WL (2012) New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat Rev Mol Cell Biol 13(7):411–424; Welsby I, Hutin D, Leo O (2012) Complex roles of members of the ADP-ribosyl transferase super family in immune defences: looking beyond PARP1. Biochem Pharmacol 84(1):11–20; Chambon P, Weill JD, Mandel P (1963) Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. Biochem Biophys Res Commun 11:39–43). During the past decades, researchers’ attention has mainly focused on the DNA-damage dependent PARPs and on tankyrases. In the second part of this chapter, we have chosen to present an exhaustive and thorough description of each PARP family member that has not been widely portrayed so far. For this reason, we will not describe the DNA-damage dependent PARPs, PARP-1, -2 and -3, reviewed in two other chapters of this book (Chaps. 7 and 8). We will also not detail the tankyrases TNKS1 and TNKS2, objects of a distinct chapter too (Chap. 4). We will V. Schreiber () · E. Héberlé · J.-C. Amé · G. Illuzzi · F. Dantzer Biotechnology and Cell Signalling, UMR7242 CNRS, Université de Strasbourg, IREBS, Laboratory of Excellence Medalis, Equipe Labellisée Ligue contre le Cancer, ESBS, 300 Blvd Sébastien Brant, CS 10413, 67412 Illkirch, France e-mail: [email protected] © Springer International Publishing Switzerland 2015 N. J. Curtin, R. A. Sharma (eds.), PARP Inhibitors for Cancer Therapy, Cancer Drug Discovery and Development 83, DOI 10.1007/978-3-319-14151-0_2 E. Héberlé et al. 16 highlight the possible therapeutic avenues opened by the new biological roles that emerged for these highly promising PARP family members but still rather poorly characterized.