The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-κB in inflammatory disorders
- P. O. HassaAffiliated withInstitute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland), Fax + 41 1 635 68 40, e-mail: firstname.lastname@example.org
- , M. O. HottigerAffiliated withInstitute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland), Fax + 41 1 635 68 40, e-mail: email@example.com
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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 β-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-κB) have both been suggested to play a crucial role in inflammatory disorders. NF-κB 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-κB. 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-κB. A more precise role for PARP-1 in NF-κB-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.
- The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-κB in inflammatory disorders
Cellular and Molecular Life Sciences CMLS
Volume 59, Issue 9 , pp 1534-1553
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- Birkhäuser Verlag
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- Key words. PARP-1; NF-κB; coactivator; positive cofactor; inflammatory response; endotoxin; septic shock; diabetes; peroxynitrite.
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