Clarke S L, Robinson C E, Gimble J M
Immunobiology & Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Biochem Biophys Res Commun. 1997 Nov 7;240(1):99-103. doi: 10.1006/bbrc.1997.7627.
The CCAAT/enhancer binding proteins (C/EBPs) and the peroxisome proliferator-activated receptors (PPARs) together regulate adipogenesis. The current work uses co-transfection studies to examine the C/ EBP dependence of PPAR gamma 2 transcription. Both C/ EBP alpha and C/EBP delta expression vectors activated transcription from a PPAR gamma 2 promoter/luciferase expression vector by 5-6 fold in UMR106 cells. The simultaneous transfection of the C/EBP homologous protein (CHOP) (also known as growth arrest DNA damage protein 153 or gadd153) inhibited this C/EBP-dependent activation in a concentration dependent manner. The CHOP protein is known to heterodimerize with other C/EBP proteins to form transcriptionally inactive complexes. Mutation of the two C/EBP DNA recognition elements at -340 bp and -327 bp within the PPAR gamma 2 promoter reduced the inductive effects of both C/EBP alpha and C/EBP delta. These findings demonstrate that proteins within the C/EBP family directly modulate transcription from the PPAR gamma 2 promoter.
CCAAT/增强子结合蛋白(C/EBP)和过氧化物酶体增殖物激活受体(PPAR)共同调节脂肪生成。目前的研究利用共转染实验来检测PPARγ2转录对C/EBP的依赖性。在UMR106细胞中,C/EBPα和C/EBPδ表达载体均可使PPARγ2启动子/荧光素酶表达载体的转录激活5至6倍。同时转染C/EBP同源蛋白(CHOP)(也称为生长停滞DNA损伤蛋白153或gadd153)会以浓度依赖的方式抑制这种C/EBP依赖性激活。已知CHOP蛋白可与其他C/EBP蛋白形成异二聚体,从而形成转录无活性的复合物。PPARγ2启动子中-340 bp和-327 bp处的两个C/EBP DNA识别元件发生突变,会降低C/EBPα和C/EBPδ的诱导作用。这些发现表明,C/EBP家族中的蛋白质可直接调节PPARγ2启动子的转录。