Identification and Characterization of a Novel Transcriptional Activation Domain in the CREB-binding Protein*
Identification and Characterization of a Novel Transcriptional Activation Domain in the CREB-binding Protein*
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CREB 结合蛋白中新型转录激活结构域的鉴定和表征*
DOI：
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发表时间：
1996
影响因子：
4.8
通讯作者：
R. Rehfuss
中科院分区：
文献类型：
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作者：
S. Bisotto;Stephanie Minorgan;R. Rehfuss
CREB 结合蛋白 (CBP) 在通过几种不同的第二信使途径（包括血清生长因子、cAMP 和佛波酯）调节基因表达中发挥着核心作用。 CBP 特异性结合 CREB 和 c-Jun 的磷酸化形式，并被认为通过 C 端激活结构域激活转录。在本报告中，我们证明 CBP 的 C 末端对于刺激磷酸化 CREB 活性的能力来说是可有可无的，而且，进一步删除该结构域会产生高活性的 CBP 突变形式。通过该缺失分析鉴定出的新型 N 端激活由 CBP 的前 714 个氨基酸组成，足以实现高水平的转录活性。该结构域还能够刺激第二种 cAMP 调节因子 ATF-1 的活性。令人惊讶的是，全长 CBP 并未显着刺激 ATF-1 活性，这表明 CBP 的 C 末端结构域也可能起到调节 ATF-1/CBP 活性的作用。此外，证明我们的一个高度活跃的 CBP 突变体能够激活 CREB 的非磷酸化突变体 (M1 CREB)，这提供了 CBP 可能在调节 CREB 基础转录活性中发挥作用的第一个证据。
The CREB-binding protein (CBP) plays a central role in the regulation of gene expression by several different second messenger pathways including serum growth factors, cAMP and phorbol esters. CBP specifically binds to the phosphorylated forms of CREB and c-Jun and is thought to activate transcription through a C-terminal activation domain. In this report, we demonstrate that the C terminus of CBP is dispensable for its ability to stimulate phospho-CREB activity, and, further, that the deletion of this domain produces highly active, mutant forms of CBP. The novel N-terminal activation identified by this deletional analysis consists of the first 714 amino acids of CBP and is sufficient for high levels of transcriptional activity. This domain is also capable of stimulating the activity of a second cAMP-regulated factor, ATF-1. Surprisingly, ATF-1 activity is not significantly stimulated by full-length CBP suggesting that the C-terminal domain of CBP may also serve to regulate ATF-1/CBP activity. Additionally, the demonstration that one of our hyperactive CBP mutants is able to activate a nonphosphorylatable mutant of CREB (M1 CREB) provides the first evidence that CBP may play a role in regulating the basal transcriptional activity of CREB.
影响因子：
10.5
作者：
LEE, JS;GALVIN, KM;SHI, Y
通讯作者：
SHI, Y