机构：[1]Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology/Shanghai Key Laboratoryfor Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China[2]Institute of Cancer Stem cells, Dalian MedicalUniversity Cancer Center, Liaoning, China[3]Digestive Endoscopy Center, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China[4]Department of Endocrinology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China[5]Institute of Biomedical Sciences, East China NormalUniversity, Shanghai, 200241, China[6]Department of Biological Sciences, Florida Atlantic University, 777 Glades Road, Boca Raton 33431, FL, USA[7]Wistar Institute, 3601Spruce Street, Philadelphia, 19104, PA, USA[8]Department of Cell Biology, Dalian Medical University, Liaoning, China
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 PPAR gamma. Ajuba binds the DNA-binding domain of PPAR gamma via its preLIM region in a ligand-independent manner. Depletion of Ajuba in 3T3-L1 cells decreases PPAR gamma target gene expression and results in delayed adipogenic differentiation. Conversely, stable overexpression of Ajuba in 3T3-L1 cells increases PPAR gamma 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 PPAR gamma. Moreover, Ajuba, PPAR gamma, p300/CBP can cooperatively occupy the PPAR gamma target promoters and concomitantly increases histone acetylation at these loci. Collectively, these data suggest that Ajuba is a co-activator constitutively associated with PPAR gamma and may be a potential therapeutic target for PPAR gamma-mediated metabolic disorders.
基金：
Ministry of Sciences and Technology of ChinaMinistry of Science and Technology, China [2013CB 910900]; National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81172028, 81372309]; Shanghai Committee of Science and TechnologyShanghai Science & Technology Committee [13JC1401302]; Shanghai Municipal Commission of Health and Family Planning [201440426]; Science and Technology Commission of Changning District of Shanghai [CNKW2014F01]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA010815] Funding Source: NIH RePORTER
第一作者机构：[1]Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology/Shanghai Key Laboratoryfor Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China[2]Institute of Cancer Stem cells, Dalian MedicalUniversity Cancer Center, Liaoning, China
共同第一作者：
通讯作者：
通讯机构：[1]Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology/Shanghai Key Laboratoryfor Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China[2]Institute of Cancer Stem cells, Dalian MedicalUniversity Cancer Center, Liaoning, China[7]Wistar Institute, 3601Spruce Street, Philadelphia, 19104, PA, USA[8]Department of Cell Biology, Dalian Medical University, Liaoning, China[*1]Wistar Institute, 3601 Spruce Street, Philadelphia, 19104, PA, USA[*2]9 Western Section, Lvshun South Street, Dalian 116044, China[*3]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, 280 South Chongqing Road, Building 7#, Room 110, Shanghai 200025, China
推荐引用方式(GB/T 7714)：
Li Q.,Peng H.,Fan H.,et al.The LIM protein Ajuba promotes adipogenesis by enhancing PPAR gamma and p300/CBP interaction[J].CELL DEATH AND DIFFERENTIATION.2016,23(1):158-168.doi:10.1038/cdd.2015.83.
APA：
Li, Q.,Peng, H.,Fan, H.,Zou, X.,Liu, Q....&Hou, Z..(2016).The LIM protein Ajuba promotes adipogenesis by enhancing PPAR gamma and p300/CBP interaction.CELL DEATH AND DIFFERENTIATION,23,(1)
MLA：
Li, Q.,et al."The LIM protein Ajuba promotes adipogenesis by enhancing PPAR gamma and p300/CBP interaction".CELL DEATH AND DIFFERENTIATION 23..1(2016):158-168
生物学