The PARP superfamily.
Poly(ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins that contributes to the survival of injured proliferating cells. Poly(ADP-ribose) polymerases (PARPs) now constitute a large family of 18 proteins, encoded by different genes and displaying a conserved catalytic domain in which PARP-1 (113 kDa), the founding member, and PARP-2 (62 kDa) are so far the sole enzymes whose catalytic activity has been shown to be immediately stimulated by DNA strand breaks. A large repertoire of sequences encoding novel PARPs now extends considerably the field of poly(ADP-ribosyl)ation reactions to various aspects of the cell biology including cell proliferation and cell death. Some of these new members interact with each other, share common partners and common subcellular localizations suggesting possible fine tuning in the regulation of this post-translational modification of proteins. This review summarizes our present knowledge of this emerging superfamily, which might ultimately improve pharmacological strategies to enhance both antitumor efficacy and the treatment of a number of inflammatory and neurodegenerative disorders. A provisional nomenclature is proposed.
Unité 9003 du CNRS, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France.
Jean-Christophe
JC
Amé
Catherine
C
Spenlehauer
Gilbert
G
de Murcia
D000595:Amino Acid Sequence; D000818:Animals; D051033:Apoptosis Inducing Factor; D020134:Catalytic Domain; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D005420:Flavoproteins / Q000378:metabolism; D016678:Genome; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D011065:Poly(ADP-ribose) Polymerases / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D011487:Protein Conformation; D016415:Sequence Alignment; D008941:Spindle Apparatus; D000076105:X-ray Repair Cross Complementing Protein 1
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D004268:DNA-Binding Proteins; D005420:Flavoproteins; D008565:Membrane Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; D011065:Poly(ADP-ribose) Polymerases