Leonard J, Serup P, Gonzalez G, Edlund T, Montminy M
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6247-51. doi: 10.1073/pnas.89.14.6247.
Many eukaryotic genes are regulated by cAMP through a conserved cAMP response element (CRE). Here we show that, in the pancreatic islet cell line Tu6, a well-characterized CRE in the somatostatin gene does not provide cAMP responsiveness but functions as an essential element for its basal activity. DNA-binding and functional analyses indicate that the cAMP-responsive factor CREB regulates somatostatin expression in these cells without requirement for phosphorylation at the protein kinase A-regulated Ser-133 phosphorylation site. In addition to the CRE site, cell-specific expression of the somatostatin gene requires a second promoter element, which binds the recently characterized LIM family protein Isl-1. Thus, Isl-1 and CREB appear to synergize on the somatostatin promoter to stimulate high-level expression in Tu6 cells. The ability of CREB to function in a phosphorylation-independent manner suggests a mechanism by which this protein can regulate gene transcription.
许多真核基因通过保守的环磷酸腺苷反应元件（CRE）受环磷酸腺苷（cAMP）调控。在此我们表明，在胰岛细胞系Tu6中，生长抑素基因中一个特征明确的CRE并不赋予cAMP反应性，而是作为其基础活性的必需元件发挥作用。DNA结合和功能分析表明，cAMP反应因子CREB在这些细胞中调节生长抑素表达，而无需蛋白激酶A调控的Ser-133磷酸化位点的磷酸化。除了CRE位点外，生长抑素基因的细胞特异性表达还需要第二个启动子元件，该元件与最近鉴定的LIM家族蛋白Isl-1结合。因此，Isl-1和CREB似乎在生长抑素启动子上协同作用，以刺激Tu6细胞中的高水平表达。CREB以不依赖磷酸化的方式发挥作用的能力提示了该蛋白调控基因转录的一种机制。
