The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders.
Mammalian poly(ADP-ribose)polymerase 1 (PARP-1) is an abundant nuclear chromatin-associated protein and belongs to a large family of enzymes that catalyzes the transfer of ADP-ribose units from its substrate beta-nicotinamide adenine dinucleotide (NAD+) covalently to itself and other nuclear chromatin-associated proteins. PARP-1 knockout mice are protected against myocardial infarction, streptozotocin-induced diabetes, lipopolysaccharide-induced septic shock, and zymosan-induced multiple organ failure, indicating that PARP-1 is involved in the regulation of the pathogenesis of these disorders. PARP-1 and nuclear factor kappa B (NF-kappaB) have both been suggested to play a crucial role in inflammatory disorders. NF-kappaB encompasses a family of inducible transcription factors which play a crucial role in the regulation of genes involved in immune and inflammatory responses. Recent reports have shown that PARP-1 can act as a coactivator of NF-kappaB. These findings might provide new insights into the pathophysiology of different diseases such as type I diabetes and septic shock. The purpose of this review is to give a short overview of the current knowledge about PARP-1 and its functional and biochemical interactions with NF-kappaB. A more precise role for PARP-1 in NF-kappaB-dependent gene regulation and cellular metabolism during development of pathophysiological processes is discussed. Special considerations is given to the pathophysiological significance of these findings in terms of inflammatory disorders.
Hassa
P O
PO
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Switzerland.
Hottiger
M O
MO
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009102:Multiple Organ Failure / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D009336:Necrosis; D009369:Neoplasms / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000502:physiology*; D012772:Shock, Septic / Q000378:metabolism; D014018:Tissue Distribution
D016328:NF-kappa B; D011065:Poly(ADP-ribose) Polymerases