Coactivator function of RIP140 for NFkappaB/RelA-dependent cytokine gene expression.
Inflammatory responses represent a hallmark of numerous pathologies including sepsis, bacterial infection, insulin resistance, and malign obesity. Here we describe an unexpected coactivator function for the nuclear receptor interacting protein 140 (RIP140) for nuclear factor kappaB (NFkappaB), a master transcriptional regulator of inflammation in multiple tissues. Previous work has shown that RIP140 suppresses the expression of metabolic gene networks, but we have found that genetic as well as acute deficiency of RIP140 leads to the inhibition of the proinflammatory program in macrophages. The ability of RIP140 to function as a coactivator for cytokine gene promoter activity relies on direct protein-protein interactions with the NFkappaB subunit RelA and histone acetylase cAMP-responsive element binding protein (CREB)-binding protein (CBP). RIP140-dependent control of proinflammatory gene expression via RelA/CBP may, therefore, represent a molecular rational for the cellular integration of metabolic and inflammatory pathways.
Zschiedrich
Inka
I
Emmy Noether and Marie Curie Research Group Molecular Metabolic Control, German Cancer Research Center Heidelberg, Heidelberg, Germany.
Hardeland
Ulrike
U
Krones-Herzig
Anja
A
Berriel Diaz
Mauricio
M
Vegiopoulos
Alexandros
A
Müggenburg
Johannes
J
Sombroek
Dirk
D
Hofmann
Thomas G
TG
Zawatzky
Rainer
R
Yu
Xiaolei
X
Gretz
Norbert
N
Christian
Mark
M
White
Roger
R
Parker
Malcolm G
MG
Herzig
Stephan
S
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1; D011485:Protein Binding / Q000276:immunology; D051996:Transcription Factor RelA / Q000276:immunology / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D016328:NF-kappa B; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D051996:Transcription Factor RelA; D050882:CREB-Binding Protein