title: Transcriptional activation of PIK3R1 by PPARγ in adipocytes.
abstract: Phosphatidylinositol 3-kinase (PI3K) plays an important role in the metabolic actions of insulin and is required for adipogenesis. Regulatory subunit 1 of PI3K (PIK3R1) is a critical component of the PI3K signaling pathway. Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipogenesis. Although the PPARγ agonist rosiglitazone induces the expression of PIK3R1, the transcriptional regulation of PIK3R1 in adipocytes remains unknown. In this study, we investigated whether PIK3R1 is a direct target of PPARγ. The level of PIK3R1 expression in 3T3-L1 cells was increased after the induction of adipocyte differentiation and was also induced by overexpression of PPARγ. Furthermore, the upregulation of PPARγ-mediated PIK3R1 expression enhanced the insulin-stimulated AKT activation in 3T3-L1 cells. Two putative peroxisome proliferator response elements (PPREs) in the PIK3R1 promoter were identified as PPARγ binding sites. By chromatin immunoprecipitation, we observed that PPARγ interacts with the two PPRE regions of the PIK3R1 promoter in mature adipocytes. In addition, luciferase reporter assays showed that the -1183/-1161 and -573/-551 regions of the PIK3R1 promoter contain essential elements for PPARγ binding. Taken together, these results suggest that PPARγ is essential for the transcriptional activity of PIK3R1 during adipogenesis.
authors.affiliation: Department of Biology, Research Institute for Basic Science, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ki Yong
authors.initials: KY
authors.lastname: Chung
authors.forename: Inho
authors.initials: I
authors.lastname: Choi
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; C579635:Pik3ip1 protein, mouse