Gurney A L, Park E A, Giralt M, Liu J, Hanson R W
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
J Biol Chem. 1992 Sep 5;267(25):18133-9.
Jun homodimers and Fos/Jun heterodimers bind to the gene for phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) at three sites within the first 350 base pairs of the promoter. These include CRE-1 (-82 to -90), and P3(II) and P4 (-252 to -258 and -268 to -285, respectively). Over-expression of Jun in HepG2 cells resulted in a 10-15-fold increase in the level of transcription of a chimeric PEPCK (-490 to +73)-CAT gene, while expression of Fos decreased transcription and blocked the induction of transcription from the PEPCK promoter by Jun. The action of Fos and Jun on PEPCK gene transcription involved each of the Fos/Jun-binding sites and was modulated by additional transcriptional regulatory elements within the PEPCK promoter. The ability of Fos to inhibit PEPCK transcription was dependent upon P3(I), a region of the promoter which does not bind Fos/Jun heterodimers, but does bind members of the C/EBP family of transcription factors. Stimulation of PEPCK transcription by 8-Br-cAMP or by overexpression of the catalytic subunit of protein kinase A was inhibited by Fos expression. The inhibitory effects of phorbol esters and protein kinase C on PEPCK gene expression may be mediated through the action of Fos and Jun.
Jun 同二聚体和 Fos/Jun 异二聚体在磷酸烯醇式丙酮酸羧激酶（GTP）（EC 4.1.1.32）（PEPCK）基因启动子的前 350 个碱基对内的三个位点结合。这些位点包括 CRE-1（-82 至 -90）、P3(II) 和 P4（分别为 -252 至 -258 和 -268 至 -285）。在 HepG2 细胞中过表达 Jun 导致嵌合的 PEPCK（-490 至 +73）-CAT 基因转录水平增加 10 - 15 倍，而 Fos 的表达则降低转录并阻断 Jun 对 PEPCK 启动子转录的诱导。Fos 和 Jun 对 PEPCK 基因转录的作用涉及每个 Fos/Jun 结合位点，并受到 PEPCK 启动子内其他转录调节元件的调节。Fos 抑制 PEPCK 转录的能力取决于 P3(I)，这是启动子的一个区域，它不结合 Fos/Jun 异二聚体，但能结合转录因子 C/EBP 家族的成员。8-Br-cAMP 或蛋白激酶 A 催化亚基的过表达对 PEPCK 转录的刺激被 Fos 的表达所抑制。佛波酯和蛋白激酶 C 对 PEPCK 基因表达的抑制作用可能是通过 Fos 和 Jun 的作用介导的。
