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Inhibition of NF-kappa B by S-nitrosylation.

Publication ,  Journal Article
Marshall, HE; Stamler, JS
Published in: Biochemistry
February 13, 2001

It is not clear if redox regulation of transcription is the consequence of direct redox-related modifications of transcription factors, or if it occurs at some other redox-sensitive step. One obstacle has been the inability to demonstrate redox-related modifications of transcription factors in vivo. The redox-sensitive transcriptional activator NF-kappaB (p50-p65) is a case in point. Its activity in vitro can be inhibited by S-nitrosylation of a critical thiol in the DNA-interacting p50 subunit, but modulation of NF-kappaB activity by nitric oxide synthase (NOS) has been attributed to other mechanisms. Herein we show that cellular NF-kappaB activity is in fact regulated by S-nitrosylation. We observed that both S-nitrosocysteine and cytokine-activated NOS2 inhibited NF-kappaB in human respiratory cells or murine macrophages. This inhibition was reversed by addition of the denitrosylating agent dithiothreitol to cellular extracts, whereas NO bioactivity did not affect the TNFalpha-induced degradation of IkappaBalpha or the nuclear translocation of p65. Recapitulation of these conditions in vitro resulted in S-nitrosylation of recombinant p50, thereby inhibiting its binding to DNA, and this effect was reversed by dithiothreitol. Further, an increase in S-nitrosylated p50 was detected in cells, and the level was modulated by TNFalpha. Taken together, these data suggest that S-nitrosylation of p50 is a physiological mechanism of NF-kappaB regulation.

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Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

February 13, 2001

Volume

40

Issue

6

Start / End Page

1688 / 1693

Location

United States

Related Subject Headings

  • Transfection
  • Transcription, Genetic
  • S-Nitrosothiols
  • Protein Binding
  • Nitroso Compounds
  • Nitrosation
  • Nitric Oxide Synthase
  • NF-kappa B p50 Subunit
  • NF-kappa B
  • NF-KappaB Inhibitor alpha
 

Citation

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Marshall, H. E., & Stamler, J. S. (2001). Inhibition of NF-kappa B by S-nitrosylation. Biochemistry, 40(6), 1688–1693. https://doi.org/10.1021/bi002239y
Marshall, H. E., and J. S. Stamler. “Inhibition of NF-kappa B by S-nitrosylation.Biochemistry 40, no. 6 (February 13, 2001): 1688–93. https://doi.org/10.1021/bi002239y.
Marshall HE, Stamler JS. Inhibition of NF-kappa B by S-nitrosylation. Biochemistry. 2001 Feb 13;40(6):1688–93.
Marshall, H. E., and J. S. Stamler. “Inhibition of NF-kappa B by S-nitrosylation.Biochemistry, vol. 40, no. 6, Feb. 2001, pp. 1688–93. Pubmed, doi:10.1021/bi002239y.
Marshall HE, Stamler JS. Inhibition of NF-kappa B by S-nitrosylation. Biochemistry. 2001 Feb 13;40(6):1688–1693.
Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

February 13, 2001

Volume

40

Issue

6

Start / End Page

1688 / 1693

Location

United States

Related Subject Headings

  • Transfection
  • Transcription, Genetic
  • S-Nitrosothiols
  • Protein Binding
  • Nitroso Compounds
  • Nitrosation
  • Nitric Oxide Synthase
  • NF-kappa B p50 Subunit
  • NF-kappa B
  • NF-KappaB Inhibitor alpha