Chrivia J C, Kwok R P, Lamb N, Hagiwara M, Montminy M R, Goodman R H
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Nature. 1993 Oct 28;365(6449):855-9. doi: 10.1038/365855a0.
Cyclic AMP-regulated gene expression frequently involves a DNA element known as the cAMP-regulated enhancer (CRE). Many transcription factors bind to this element, including the protein CREB, which is activated as a result of phosphorylation by protein kinase A. This modification stimulates interaction with one or more of the general transcription factors or, alternatively, allows recruitment of a co-activator. Here we report that CREB phosphorylated by protein kinase A binds specifically to a nuclear protein of M(r) 265K which we term CBP (for CREB-binding protein). Fusion of a heterologous DNA-binding domain to the amino terminus of CBP enables the chimaeric protein to function as a protein kinase A-regulated transcriptional activator. We propose that CBP may participate in cAMP-regulated gene expression by interacting with the activated phosphorylated form of CREB.
环磷酸腺苷（cAMP）调节的基因表达通常涉及一种被称为cAMP调节增强子（CRE）的DNA元件。许多转录因子会结合到该元件上，包括蛋白CREB，它会因蛋白激酶A的磷酸化作用而被激活。这种修饰会刺激与一种或多种通用转录因子的相互作用，或者允许募集共激活因子。在此，我们报告称，被蛋白激酶A磷酸化的CREB会特异性地结合到一种分子量为265K的核蛋白上，我们将其命名为CBP（CREB结合蛋白）。将异源DNA结合结构域融合到CBP的氨基末端，可使嵌合蛋白作为一种受蛋白激酶A调节的转录激活因子发挥作用。我们提出，CBP可能通过与CREB的激活磷酸化形式相互作用来参与cAMP调节的基因表达。
