Nucleic Acids Research, Vol 24, Issue 12 2236-2242, Copyright © 1996 by Oxford University Press
JR Matthews, CH Botting, M Panico, HR Morris and RT Hay
It has been suggested that the NF-kappaB transcription factor family may
mediate expression of the gene encoding the cytokine-inducible form of
nitric oxide synthase (iNOS). To establish if nitric oxide (NO) could in
turn affect activity of NF-kappaB, the ability of NO-donor compounds to
influence NF-kappaB DNA binding activity in vitro was investigated.
NO-donor compounds sodium nitroprusside (SNP) and S-
nitroso-N-acetylpenicillamine (SNAP) both inhibited the DNA binding
activity of recombinant NF-kappaB p50 and p65 homodimers and of p50-p65
heterodimers. Inhibition of NF-kappaB p50 DNA binding by NO-donor compounds
involved modification of the conserved redox-sensitive C62 residue, as a
C62S p50 mutant was significantly more resistant to SNP- mediated
inactivation. Non-reducing SDS-polyacrylamide gel electrophoresis
demonstrated that SNP could inhibit p50 DNA binding by mechanisms other
than the formation of intersubunit disulphide bonds involving p50 residue
C62. Electrospray ionization mass spectrometry of a synthetic NF-kappaB p5O
peptide containing the C62 residue suggested that NO gas can modify C62 by
S-nitrosylation. This study indicates that NO-donors can directly inhibit
the DNA binding activity of NF- kappaB family proteins, suggesting that
cellular NO provides another control mechanism for modulating the
expression of NF-kappaB-responsive genes.
ARTICLES
Inhibition of NF-kappaB DNA binding by nitric oxide
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M. Maccarrone, M. van der Stelt, A. Rossi, G. A. Veldink, J. F. G. Vliegenthart, and A. F. Agro Anandamide Hydrolysis by Human Cells in Culture and Brain J. Biol. Chem., November 27, 1998; 273(48): 32332 - 32339. [Abstract] [Full Text] [PDF]
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K. Sogawa, K. Numayama-Tsuruta, M. Ema, M. Abe, H. Abe, and Y. Fujii-Kuriyama Inhibition of hypoxia-inducible factor 1 activity by nitric oxide donors in hypoxia PNAS, June 23, 1998; 95(13): 7368 - 7373. [Abstract] [Full Text] [PDF]
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D. Sekkai, F. Aillet, N. Israel, and M. Lepoivre Inhibition of NF-kappa B and HIV-1 Long Terminal Repeat Transcriptional Activation by Inducible Nitric Oxide Synthase 2 Activity J. Biol. Chem., February 13, 1998; 273(7): 3895 - 3900. [Abstract] [Full Text] [PDF]
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H. Togashi, M. Sasaki, E. Frohman, E. Taira, R. R. Ratan, T. M. Dawson, and V. L. Dawson Neuronal (type I) nitric oxide synthase regulates nuclear factorkappa B activity and immunologic (type II) nitric oxide synthase expression PNAS, March 18, 1997; 94(6): 2676 - 2680. [Abstract] [Full Text] [PDF]
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E. Cernuda-Morollon, E. Pineda-Molina, F. J. Canada, and D. Perez-Sala 15-Deoxy-Delta 12,14-prostaglandin J2 Inhibition of NF-kappa B-DNA Binding through Covalent Modification of the p50 Subunit J. Biol. Chem., September 14, 2001; 276(38): 35530 - 35536. [Abstract] [Full Text] [PDF]
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