Physiology and pathophysiology of poly(ADP‐ribosyl)ation *
- 27 August 2001
- Vol. 23 (9), 795-806
- https://doi.org/10.1002/bies.1115
Abstract
One of the immediate eukaryotic cellular responses to DNA breakage is the covalent post‐translational modification of nuclear proteins with poly(ADP‐ribose) from NAD+ as precursor, mostly catalysed by poly(ADP‐ribose) polymerase‐1 (PARP‐1). Recently several other polypeptides have been shown to catalyse poly(ADP‐ribose) formation. Poly(ADP‐ribosyl)ation is involved in a variety of physiological and pathophysiological phenomena. Physiological functions include its participation in DNA‐base excision repair, DNA‐damage signalling, regulation of genomic stability, and regulation of transcription and proteasomal function, supporting the previously observed correlation of cellular poly(ADP‐ribosyl)ation capacity with mammalian life. The pathophysiology effects are mediated through PARP‐1 overactivity, which can cause cell suicide by NAD+ depletion. It is apparent that the latter effect underlies the pathogenesis of a wide range of disease states including type‐1 diabetes, ischaemic infarcts in various organs, and septic or haemorrhagic shock. Therefore pharmacological modulation of poly(ADP‐ribosyl)ation may prove to be an exciting option for various highly prevalent, disabling and even lethal diseases. BioEssays 23:795–806, 2001. © 2001 John Wiley & Sons, Inc.Keywords
This publication has 66 references indexed in Scilit:
- Caspase-3-mediated Processing of Poly(ADP-ribose) Glycohydrolase during ApoptosisJournal of Biological Chemistry, 2001
- Tankyrase Is a Golgi-associated Mitogen-activated Protein Kinase Substrate That Interacts with IRAP in GLUT4 VesiclesPublished by Elsevier ,2000
- GPI 6150 Prevents H2O2 Cytotoxicity by Inhibiting Poly(ADP-ribose) PolymeraseBiochemical and Biophysical Research Communications, 2000
- Apoptosis in the Dorsal Lateral Geniculate Nucleus after Monocular Deprivation Involves Glutamate Signaling, NO Production, and PARP ActivationBiochemical and Biophysical Research Communications, 2000
- ATP for the DNA Ligation Step in Base Excision Repair Is Generated from Poly(ADP-ribose)Published by Elsevier ,2000
- Characterization of sPARP-1Journal of Biological Chemistry, 2000
- Inhibition of Homodimerization of Poly(ADP-ribose) Polymerase by Its C-terminal Cleavage Products Produced during ApoptosisPublished by Elsevier ,2000
- Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factorOncogene, 1999
- Functional Interaction of Poly(ADP-ribose) with the 20S Proteasome in VitroBiochemical and Biophysical Research Communications, 1999
- Nicotinamide mononucleotide activation of a new DNA-dependent polyadenylic acid synthesizing nuclear enzymeBiochemical and Biophysical Research Communications, 1963