Poly(adenosine diphosphate-ribose) polymerase as therapeutic target: lessons learned from its inhibitors
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Anna Mária Cseh1,2, Zsolt Fábián3, Balázs Sümegi1 and Luca Scorrano2
1Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary
2Department of Biology, University of Padova, Padova, Italy
3Conway Institute, University College Dublin, Belfield, Dublin, Ireland
Anna Mária Cseh, email: firstname.lastname@example.org
Keywords: PARP, mitochondria, cancer, signaling, targeted therapy
Received: February 10, 2017 Accepted: March 28, 2017 Published: April 05, 2017
Poly(ADP-ribose) polymerases are a family of DNA-dependent nuclear enzymes catalyzing the transfer of ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide to a variety of target proteins. Although they have been considered as resident nuclear elements of the DNA repair machinery, recent works revealed a more intricate physiologic role of poly(ADP-ribose) polymerases with numerous extranuclear activities. Indeed, poly(ADP-ribose) polymerases participate in fundamental cellular processes like chromatin remodelling, transcription or regulation of the cell-cycle. These new insight into the physiologic roles of poly(ADP-ribose) polymerases widens the range of human pathologies in which pharmacologic inhibition of these enzymes might have a therapeutic potential. Here, we overview our current knowledge on extranuclear functions of poly(ADP-ribose) polymerases with a particular focus on the mitochondrial ones and discuss potential fields of future clinical applications.
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