The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders.
Cell Mol Life Sci
; 59(9): 1534-53, 2002 Sep.
Article
em En
| MEDLINE
| ID: mdl-12440774
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
/
Poli(ADP-Ribose) Polimerases
/
Inflamação
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Mol Life Sci
Ano de publicação:
2002
Tipo de documento:
Article