IKK phosphorylates RelB to modulate its promoter specificity and promote fibroblast migration downstream of TNF receptors

Authier Helene; Billot Katy; Derudder EmmanuelBordereaux DidierRiviere PierreRodrigues-Ferreira SylvieNahmias ClaraBaud Veronique

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IKK phosphorylates RelB to modulate its promoter specificity and promote fibroblast migration downstream of TNF receptors

机译：IKK phosphorylates RelB to modulate its promoter specificity and promote fibroblast migration downstream of TNF receptors

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TNF alpha is a potent cytokine that plays a critical role in numerous cellular processes, particularly immune and inflammatory responses, programmed cell death, angiogenesis, and cell migration. Thus, understanding the molecular mechanisms that mediate TNF alpha-induced cellular responses is a crucial issue. It is generally accepted that global DNA binding activity of the NF-kappa B avian reticuloendotheliosis viral (v-rel) oncogene related B (RelB) subunit is not induced upon TNFa treatment in fibroblasts, despite its TNF alpha-induced nuclear accumulation. Here, we demonstrate that RelB plays a critical role in promoting fibroblast migration upon prolonged TNF alpha treatment. We identified the two kinases I kappa B kinase a (IKK alpha) and I kappa B kinase beta (IKK beta) as RelB interacting partners whose activation by TNF alpha promotes RelB phosphorylation at serine 472. Once phosphorylated on serine 472, nuclear RelB dissociates from its interaction with the inhibitory protein I kappa B alpha and binds to the promoter of critical migration-associated genes, such as the matrix metallopeptidase 3 (MMP3). Further, we show that RelB serine 472 phosphorylation status controls MMP3 expression and promigration activity downstream of TNF receptors. Our findings provide new insights into the regulation of RelB activity and reveal a novel link between selective NF-kappa B target gene expression and cellular response in response to TNF alpha.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第41期|14794-14799|共6页
作者
Authier Helene; Billot Katy; Derudder EmmanuelBordereaux DidierRiviere PierreRodrigues-Ferreira SylvieNahmias ClaraBaud Veronique;
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作者单位

Inst Cochin, U1016, INSERM, F-75014 Paris, France;

Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
TNFalpha; NF-kappaB; metalloproteinase; posttranslational modification;

IKK phosphorylates RelB to modulate its promoter specificity and promote fibroblast migration downstream of TNF receptors

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