The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Nitric oxide represses inhibitory κB kinase through S-nitrosylation
Open accessAbstract
Nitric oxide (NO) possesses antiinflammatory effects, which may be exerted via its ability to inhibit the transcription factor, NF-κB. A commonly proposed mode of action for inhibition of NF-κBbyNO involves interference with NF-κB binding to DNA. Because activation of inhibitory κB kinase (IKK), the prerequisite enzyme complex necessary to induce NF-κB, is subject to redox regulation, we assessed whether IKK could present a more proximal target for NO to inhibit NF-κB activation. We demonstrate here that S -nitrosothiols (SNO) caused a dose-dependent inhibition of the enzymatic activity of IKK, in lung epithelial cells and in Jurkat T cells, which was associated with S-nitrosylation of the IKK complex. Using biotin derivatization of SNO, we revealed that IKKβ, the catalytic subunit required for NF-κB activation, was a direct target for S-nitrosylation. A mutant version of IKKβ containing a Cys-179-to-Ala mutation was refractory to inhibition by SNO or to increases in S-nitrosylation, in contrast to wild-type IKKβ, demonstrating that Cys-179 is the main target for attack by SNO. Importantly, inhibition of NO synthase activity in Jurkat T cells resulted in activation of IKK, in association with its denitrosylation. Moreover, NO synthase inhibition enhanced the ability of tumor necrosis factor α to activate IKK, illustrating the importance of endogenous NO in regulating the extent of NF-κB activation by cytokines. Collectively, our findings demonstrate that IKKβ is an important target for the redox regulation of NF-κB by endogenous or exogenous NO, providing an additional mechanism for its antiinflammatory properties.
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Cites
Phosphorylation meets ubiquitination: the control of NF-κB activity
Karin, M., & Ben-Neriah, Y. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.621 · Cited by 4,766
Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase.
Xie, Q. W., Kashiwabara, Y., & Nathan, C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37600-7 · Cited by 2,212
Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase
Rossi, A., Kapahi, P., Natoli, G., Takahashi, T., Chen, Y., Karin, M., & Santoro, M. G. (2000) · Nature · doi:10.1038/47520 · Cited by 1,310
Stamler (2001) · doi:10.1016/s0092-8674(01)00495-0 · Cited by 1,261
Signal transduction through NF-κB
May, M. J., & Ghosh, S. (1998) · Immunology Today · doi:10.1016/s0167-5699(97)01197-3 · Cited by 1,091
Lowenstein, C. J., Alley, E. W., Raval, P., Snowman, A. M., Snyder, S. H., Russell, S. W., & Murphy, W. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9730 · Cited by 1,064
A physical and functional map of the human TNF-α/NF-κB signal transduction pathway
Bouwmeester, T., Bauch, A., Ruffner, H., Angrand, P.-O., Bergamini, G., Croughton, K., Cruciat, C., Eberhard, D., Gagneur, J., Ghidelli, S., et al. (2004) · Nature Cell Biology · doi:10.1038/ncb1086 · Cited by 1,029
IKK-γ is an essential regulatory subunit of the IκB kinase complex
Rothwarf, D. M., Zandi, E., Natoli, G., & Karin, M. (1998) · Nature · doi:10.1038/26261 · Cited by 957
A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans
Liu, L., Hausladen, A., Zeng, M., Que, L., Heitman, J., & Stamler, J. S. (2001) · Nature · doi:10.1038/35068596 · Cited by 913
Fas-Induced Caspase Denitrosylation
Mannick, J. B., Hausladen, A., Liu, L., Hess, D. T., Zeng, M., Miao, Q. X., Kane, L. S., Gow, A. J., & Stamler, J. S. (1999) · Science · doi:10.1126/science.284.5414.651 · Cited by 742
Cited by
Crosstalk of reactive oxygen species and NF-κB signaling
Morgan, M. J., & Liu, Z.-G. (2011) · Cell Research · doi:10.1038/cr.2010.178 · Cited by 3,505
Protein S-nitrosylation: Purview and parameters
Hess, D. T., Matsumoto, A., Kim, S.-O., Marshall, H. E., & Stamler, J. S. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1569 · Cited by 2,153
Redox regulation of cell survival
Trachootham, D., Lu, W., Ogasawara, M. A., Valle, N. R.-D., & Huang, P. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1957 · Cited by 1,781
Hydrogen peroxide sensing and signaling
Veal, E. A., Day, A. M., & Morgan, B. A. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.016 · Cited by 1,604
Lingappan, K. (2018) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2017.11.002 · Cited by 1,051
Metadata
- Authors
- Reynaert, N. L., Ckless, K., Korn, S. H., Vos, N., Guala, A. S., Wouters, E. F. M., van der Vliet, A., & Janssen-Heininger, Y. M. W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-06-07
- Volume
- 101
- Issue
- 24
- Pages
- 8945-8950
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2153163382
- Cited by
- 388
- References
- 44
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- green
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