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The transcriptional corepressors SMRT and N-CoR function as silencing mediators for retinoid and thyroid hormone receptors. Here we show that SMRT and N-CoR directly interact with mSin3A, a corepressor for the Mad-Max heterodimer and a homolog of the yeast global-transcriptional repressor Sin3p. In addition, we demonstrate that the recently characterized(More)
We report here the identification of a novel cofactor, ACTR, that directly binds nuclear receptors and stimulates their transcriptional activities in a hormone-dependent fashion. ACTR also recruits two other nuclear factors, CBP and P/CAF, and thus plays a central role in creating a multisubunit coactivator complex. In addition, and unexpectedly, we show(More)
Macrophage uptake of oxidized low-density lipoprotein (oxLDL) is thought to play a central role in foam cell formation and the pathogenesis of atherosclerosis. We demonstrate here that oxLDL activates PPARgamma-dependent transcription through a novel signaling pathway involving scavenger receptor-mediated particle uptake. Moreover, we identify two of the(More)
Previous work has implicated PPAR gamma in the regulation of CD36 expression and macrophage uptake of oxidized LDL (oxLDL). We provide evidence here that in addition to lipid uptake, PPAR gamma regulates a pathway of cholesterol efflux. PPAR gamma induces ABCA1 expression and cholesterol removal from macrophages through a transcriptional cascade mediated by(More)
the presence of high concentrations of LDL (Brown and Goldstein, 1983). It is now clear that uptake of LDL by foam cells is mediated by a group of cell surface proteins termed scavenger receptors. Brown and Goldstein and * The Salk Institute for Biological Studies colleagues were the first to demonstrate that these re-† Howard Hughes Medical Institute(More)
The formation of foam cells from macrophages in the arterial wall is characterized by dramatic changes in lipid metabolism, including increased expression of scavenger receptors and the uptake of oxidized low-density lipoprotein (oxLDL). We demonstrate here that the nuclear receptor PPARgamma is induced in human monocytes following exposure to oxLDL and is(More)
Cells are constantly exposed to a large variety of lipids. Traditionally, these molecules were thought to serve as simple energy storing molecules. More recently it has been realized that they can also initiate and regulate signaling events that will decisively influence development, cellular differentiation, metabolism and related functions through the(More)
Peroxisome proliferator-activated receptor γ (PPARγ) is a lipid-activated transcription factor regulating lipid metabolism and inflammatory response in macrophages and dendritic cells (DCs). These immune cells exposed to distinct inflammatory milieu show cell type specification as a result of altered gene expression. We demonstrate here a mechanism how(More)
Non-liganded retinoic acid receptors (RARs) repress transcription of target genes by recruiting the histone deacetylase complex through a class of silencing mediators termed SMRT or N-CoR. Mutant forms of RARalpha, created by chromosomal translocations with either the PML (for promyelocytic leukaemia) or the PLZF (for promyelocytic leukaemia zinc finger)(More)
phage gene expression. Although the mechanisms by which oxidized LDL (oxLDL) regulates cellular gene expression are still poorly understood, recent work suggests that transcriptional pathways involving nuclear receptors mediate many biological effects of oxidized by providing the cell with oxidized fatty acid ligands of University of Debrecen the receptor(More)