{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:18:33Z","timestamp":1791497913996,"version":"4.3.4"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,6,15]]},"abstract":"<jats:p>\n                    Nitric oxide (NO) possesses antiinflammatory effects, which may be exerted via its ability to inhibit the transcription factor, NF-\u03baB. A commonly proposed mode of action for inhibition of NF-\u03baBbyNO involves interference with NF-\u03baB binding to DNA. Because activation of inhibitory \u03baB kinase (IKK), the prerequisite enzyme complex necessary to induce NF-\u03baB, is subject to redox regulation, we assessed whether IKK could present a more proximal target for NO to inhibit NF-\u03baB activation. We demonstrate here that\n                    <jats:italic>S<\/jats:italic>\n                    -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 IKK\u03b2, the catalytic subunit required for NF-\u03baB activation, was a direct target for S-nitrosylation. A mutant version of IKK\u03b2 containing a Cys-179-to-Ala mutation was refractory to inhibition by SNO or to increases in S-nitrosylation, in contrast to wild-type IKK\u03b2, 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 \u03b1 to activate IKK, illustrating the importance of endogenous NO in regulating the extent of NF-\u03baB activation by cytokines. Collectively, our findings demonstrate that IKK\u03b2 is an important target for the redox regulation of NF-\u03baB by endogenous or exogenous NO, providing an additional mechanism for its antiinflammatory properties.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0400588101","type":"journal-article","created":{"date-parts":[[2004,6,7]],"date-time":"2004-06-07T21:09:33Z","timestamp":1086642573000},"page":"8945-8950","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":347,"title":["Nitric oxide represses inhibitory \u03baB kinase through S-nitrosylation"],"prefix":"10.1073","volume":"101","author":[{"given":"Niki L.","family":"Reynaert","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Vermont, Burlington, VT 05405; and Department of Pulmonology, Maastricht University, Maastricht, 6229ER, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Ckless","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Vermont, Burlington, VT 05405; and Department of Pulmonology, Maastricht University, Maastricht, 6229ER, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solange H.","family":"Korn","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Vermont, Burlington, VT 05405; and Department of Pulmonology, Maastricht University, Maastricht, 6229ER, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanda","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Vermont, Burlington, VT 05405; and Department of Pulmonology, Maastricht University, Maastricht, 6229ER, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Guala","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Vermont, Burlington, VT 05405; and Department of Pulmonology, Maastricht University, Maastricht, 6229ER, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiel F. 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