title: The LIM protein Ajuba promotes adipogenesis by enhancing PPARγ and p300/CBP interaction.
abstract: Adipocytes play a vital role in energy homeostasis and adipogenesis is a hierarchically regulated cellular differentiation process, in which the precursor mesenchymal stem cells are differentiated into mature adipocytes. Here, we report Ajuba is an important regulator of adipocyte differentiation by functioning as an obligate co-activator of PPARγ. Ajuba binds the DNA-binding domain of PPARγ via its preLIM region in a ligand-independent manner. Depletion of Ajuba in 3T3-L1 cells decreases PPARγ target gene expression and results in delayed adipogenic differentiation. Conversely, stable overexpression of Ajuba in 3T3-L1 cells increases PPARγ target gene expression and accelerates adipogenic differentiation. Mechanistic investigations demonstrate that Ajuba recruits p300/CBP via its LIM domain and facilitates p300/CBP binding to PPARγ. Moreover, Ajuba, PPARγ, p300/CBP can cooperatively occupy the PPARγ target promoters and concomitantly increases histone acetylation at these loci. Collectively, these data suggest that Ajuba is a co-activator constitutively associated with PPARγ and may be a potential therapeutic target for PPARγ-mediated metabolic disorders.
authors.affiliation: Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology/Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Institute of Cancer Stem cells, Dalian Medical University Cancer Center, Liaoning, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Digestive Endoscopy Center, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Peng
authors.affiliation: Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology/Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Endocrinology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Fan
authors.affiliation: Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology/Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Zou
authors.affiliation: Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology/Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Institute of Cancer Stem cells, Dalian Medical University Cancer Center, Liaoning, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology/Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology/Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.affiliation: Digestive Endoscopy Center, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Institute of Biomedical Sciences, East China Normal University, Shanghai, 200241, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, 777 Glades Road, Boca Raton 33431, FL, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ayyanathan
authors.affiliation: Wistar Institute, 3601 Spruce Street, Philadelphia, 19104, PA, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Rauscher
authors.affiliation: Department of Cell Biology, Dalian Medical University, Liaoning, China.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology/Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Institute of Cancer Stem cells, Dalian Medical University Cancer Center, Liaoning, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Hou
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D004734:Energy Metabolism / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D050880:p300-CBP Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D060588:LIM Domain Proteins; D047495:PPAR gamma; C485607:ajuba protein, mouse; D050880:p300-CBP Transcription Factors