Co-activator function of RIP140 for NFκB/p65-dependent cytokine gene
Ontology highlight
ABSTRACT: High- and low-grade inflammatory responses represent a hallmark of numerous pathologies such as sepsis and bacterial infection or insulin resistance and obesity, respectively. Here we describe an unexpected co-activator function of receptor interacting protein (RIP) 140 for nuclear factor (NF) kB, a master transcriptional regulator of inflammation in multiple tissues. Genetic as well as acute deficiency of RIP140, which has been characterized as a co-repressor of various nuclear receptors on metabolic target genes, led to the inhibition of the proinflammatory program in macrophages, mediated by RIP140âs direct impact on cytokine gene promoter activity. Intriguingly, RIP140âs co-activator function in this setting was found to rely on direct protein-protein interactions with the NFκB subunit p65 and histone acetylase CREB-binding protein (CBP). RIP140-dependent control of proinflammatory gene expression via p65/CBP may, therefore, represent a molecular rational for the cellular integration of metabolic and inflammatory pathways. Keywords: expression profiling Gene expression profiling was done for macrophages from RIP140 knockout or wild-type mice. RNA isolation, cDNA and cRNA synthesis, and hybridization to arrays of type Mouse Genome 430 2.0 from Affymetrix (Santa Clara, CA, USA) were performed according to manufacturerâs recommendations. 3 arrays per genotype were hybridized. Microarray data were analysed based on ANOVA using a commercial software package (Micro Array Solution, version 1.0, SAS Institute, Cary, NC, USA). Standard settings were used, except the following specifications: log-linear mixed models were fitted for values of perfect-matches, with genotype considered to be constant and the array-id random. Custom CDF with Unigene based gene/transcript definitions was used to annotate the arrays.
ORGANISM(S): Mus musculus
SUBMITTER: Thomas Hofmann
PROVIDER: E-GEOD-10386 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
ACCESS DATA
