Sano Y, Tokitou F, Dai P, Maekawa T, Yamamoto T, Ishii S
Laboratory of Molecular Genetics, Tsukuba Life Science Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
J Biol Chem. 1998 Oct 30;273(44):29098-105. doi: 10.1074/jbc.273.44.29098.
The transcription factor ATF-2 (also called CRE-BP1), whose DNA-binding domain consists of a basic amino acid cluster and a leucine zipper (b-ZIP) region, binds to the cAMP response element as a homodimer or as a heterodimer with c-Jun. The amino-terminal region of ATF-2 containing the transcriptional activation domain is phosphorylated by stress-activated kinases, which leads to activation of ATF-2. We report here that CBP, which was originally identified as a co-activator of CREB, directly binds to the b-ZIP region of ATF-2 via a Cys/His-rich region termed C/H2, and potentiates trans-activation by ATF-2. The b-ZIP region of ATF-2 was previously shown to interact with the amino-terminal region intramolecularly and to inhibit trans-activating capacity. The binding of CBP to the b-ZIP region abrogates this intramolecular interaction. The adenovirus 13S E1A protein which binds to the b-ZIP region of ATF-2 also inhibited this intramolecular interaction, suggesting that both CBP and 13S E1A share a similar function as positive regulators of ATF-2. We found that the b-ZIP regions of c-Jun and CREB also interact with the C/H2 domain of CBP, suggesting that CBP acts as a regulator for a group of b-ZIP-containing proteins. These results shed light on a novel aspect of CBP function as a regulator for a group of b-ZIP-containing proteins.
转录因子ATF-2（也称为CRE-BP1），其DNA结合结构域由一个碱性氨基酸簇和一个亮氨酸拉链（b-ZIP）区域组成，以同二聚体形式或与c-Jun形成异二聚体的形式与cAMP反应元件结合。含有转录激活结构域的ATF-2氨基末端区域被应激激活激酶磷酸化，这导致ATF-2的激活。我们在此报告，最初被鉴定为CREB共激活因子的CBP，通过一个称为C/H2的富含半胱氨酸/组氨酸的区域直接与ATF-2的b-ZIP区域结合，并增强ATF-2的反式激活作用。先前已表明，ATF-2的b-ZIP区域在分子内与氨基末端区域相互作用，并抑制反式激活能力。CBP与b-ZIP区域的结合消除了这种分子内相互作用。与ATF-2的b-ZIP区域结合的腺病毒13S E1A蛋白也抑制了这种分子内相互作用，这表明CBP和13S E1A作为ATF-2的正调节因子具有相似的功能。我们发现，c-Jun和CREB的b-ZIP区域也与CBP的C/H2结构域相互作用，这表明CBP作为一组含b-ZIP蛋白的调节因子发挥作用。这些结果揭示了CBP作为一组含b-ZIP蛋白的调节因子功能的一个新方面。
