PMID:26504087

Citation	Kotla, S and Rao, GN (2015) Reactive Oxygen Species (ROS) Mediate p300-dependent STAT1 Protein Interaction with Peroxisome Proliferator-activated Receptor (PPAR)-γ in CD36 Protein Expression and Foam Cell Formation. J. Biol. Chem. 290:30306-20
Abstract	Previously, we have demonstrated that 15(S)-hydroxyeicosatetranoic acid (15(S)-HETE) induces CD36 expression involving STAT1. Many studies have shown that peroxisome proliferator-activated receptor (PPAR)-γ mediates CD36 expression. Therefore, we asked the question whether these transcriptional factors interact with each other in the regulation of CD36 expression by 15(S)-HETE. Here, we show that STAT1 interacts with PPARγ in the induction of CD36 expression and foam cell formation by 15(S)-HETE. In addition, using molecular biological approaches such as EMSA, supershift EMSA, ChIP, re-ChIP, and promoter-reporter gene assays, we demonstrate that the STAT1 and PPARγ complex binds to the STAT-binding site at -107 nucleotides in the CD36 promoter and enhances its activity. Furthermore, the interaction of STAT1 with PPARγ depends on STAT1 acetylation, which is mediated by p300. In addition, our findings show that reactive oxygen species-dependent Syk and Pyk2 stimulation is required for p300 tyrosine phosphorylation and activation. Together, these results demonstrate that an interaction between STAT1, p300, and peroxisome proliferator-activated receptor-γ is required for 15(S)-HETE-induced CD36 expression, oxidized low density lipoprotein uptake, and foam cell formation, critical events underlying the pathogenesis of atherosclerosis.
Links	PubMed PMC4683256 Online version:10.1074/jbc.M115.686865
Keywords	Atherosclerosis/metabolism; Atherosclerosis/pathology; CD36 Antigens/biosynthesis; Cell Line, Tumor; E1A-Associated p300 Protein/metabolism; Foam Cells/metabolism; Foam Cells/pathology; Gene Expression Regulation; Humans; Hydroxyeicosatetraenoic Acids/pharmacology; PPAR gamma/metabolism; Reactive Oxygen Species/metabolism; Response Elements; STAT1 Transcription Factor/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PPARA	enables	GO:0008134: transcription factor binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P42224	F		Seeded From UniProt	complete
HUMAN:PPARD	enables	GO:0008134: transcription factor binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P42224	F		Seeded From UniProt	complete
HUMAN:PPARG	enables	GO:0008134: transcription factor binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P42224	F		Seeded From UniProt	complete
HUMAN:PPARG	involved_in	GO:0010742: macrophage derived foam cell differentiation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:EP300	involved_in	GO:0010742: macrophage derived foam cell differentiation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:EP300	enables	GO:0008134: transcription factor binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P40763 UniProtKB:P42224	F		Seeded From UniProt	complete

References

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