Glutathionylation regulates IkappaB.
Although there has been considerable interest in the regulation of NFkappaB activation by glutathionylation, the possibility of IkappaB as a target for glutathionylation has not been investigated. We now report that Cys(189) of IkappaB alpha is a target for S-glutathionylation. This modification is reversed by thiols such as dithiothreitol and GSH. The glutathionylated IkappaB alpha appears to be significantly less susceptible than is native protein to phosphorylation by IkappaB kinase and casein kinase II, as well as to in vitro ubiquitination. This finding suggests that glutathionylation plays a regulatory role, presumably through structural alterations. HeLa cells treated with oxidant inducing GSH oxidation such as diamide showed the accumulation of glutathionylated IkappaB alpha. This mechanism suggests an alternative modification to the redox regulation of cysteine in IkappaB alpha and a possible mechanism in the regulation of NFkappaB activation.
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.
In Sup
IS
Kil
Sung Youl
SY
Kim
Jeen-Woo
JW
Park
D002460:Cell Line; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D054875:Ubiquitination
D020672:I-kappa B Proteins; D005978:Glutathione; D003545:Cysteine