Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 이공주 | - |
dc.date.accessioned | 2016-08-29T11:08:50Z | - |
dc.date.available | 2016-08-29T11:08:50Z | - |
dc.date.issued | 2009 | - |
dc.identifier.issn | 0006-2960 | - |
dc.identifier.other | OAK-5776 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/232003 | - |
dc.description.abstract | N-Tosyl- L-phenylalanine chloromethyl ketone (TPCK), a serine/cysteine protease inhibitor, has been reported to inhibit expression of inflammatory mediators by blocking nuclear factor-κB (NF-κB) activation. We examined the effect of TPCK on the NF-κB activation pathway in HeLa cells by measuring the activity of IκB kinase (IKK) and p65/RelA-DNA binding. TPCK inhibited tumor necrosis factor-R-induced IKK activation and directly blocked IKK activity in vitro. TPCK-induced inhibition of NF-κB and IKK activation was abrogated by addition of the thiol-reducing agent dithiothreitol, suggesting that the effect of TPCK occurred through modification of a thiol group in IKK. Consistent with this, an IKKβ mutant in which Cys-179 was substituted with alanine was not more susceptible to TPCK. Our result also showed that TPCK inhibits the DNA binding of transiently expressed p65/RelA in HeLa cells. Inhibition of p65/RelA-DNA binding was recovered in the presence of dithiothreitol, and substitution of Cys-38 with Ser in p65/RelA rendered the protein resistant to inhibition by TPCK. Mass spectrometry analysis of IKKβ and p65/RelA isolated from cells treated with TPCK by UPLC-ESI-Q-TOF tandem MS revealed the labeling of Cys-179 of IKKβ and Cys-38 of p65/RelA with a tosylphenylalanylmethyl group. These results suggest that TPCK inhibits NF-κB activation by directly modifying thiol groups on two different targets: Cys-179 of IKKβ and Cys-38 of p65/RelA. ©2009 American Chemical Society. | - |
dc.language | English | - |
dc.title | N-Tosyl-L-phenylalanine chloromethyl ketone inhibits NF-κB activation by blocking specific cysteine residues of IκB kinase β and p65/RelA | - |
dc.type | Article | - |
dc.relation.issue | 30 | - |
dc.relation.volume | 48 | - |
dc.relation.index | SCI | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 7271 | - |
dc.relation.lastpage | 7278 | - |
dc.relation.journaltitle | Biochemistry | - |
dc.identifier.doi | 10.1021/bi900660f | - |
dc.identifier.wosid | WOS:000268231800020 | - |
dc.identifier.scopusid | 2-s2.0-70350717978 | - |
dc.author.google | Ha K.-H. | - |
dc.author.google | Byun M.-S. | - |
dc.author.google | Choi J. | - |
dc.author.google | Jeong J. | - |
dc.author.google | Lee K.-J. | - |
dc.author.google | Jue D.-M. | - |
dc.contributor.scopusid | 이공주(7501497635;57191532162) | - |
dc.date.modifydate | 20230208115507 | - |