CBP-INDUCED STIMULATION OF C-FOS ACTIVITY IS ABROGATED BY E1A
CBP-INDUCED STIMULATION OF C-FOS ACTIVITY IS ABROGATED BY E1A
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DOI：
10.1002/j.1460-2075.1995.tb00157.x
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发表时间：
1995-10-02
期刊：
影响因子：
11.4
通讯作者：
KOUZARIDES, T
中科院分区：
文献类型：
--
作者：
BANNISTER, AJ;KOUZARIDES, T
CBP蛋白通过结合CREB转录因子的磷酸化激活结构域刺激cAMP应答基因的转录。在这里，我们表明，CBP刺激F9细胞中的Fos/Jun活性的转录，这种反应是介导的，至少部分地，通过c-Fos，我们表明，CBP结合c-Fos在体外磷酸化独立的方式，使用不同于所需的结合CREB的结构域。当该CBP结构域与VP 16的活化结构域连接时，它可以在体内刺激GAL 4-Fos活性。CBP结合c-Fos的结构域也用于接触E1 A蛋白，因此我们询问是否记录的E1 A对AP 1活性的抑制是由于CBP从c-Fos中的螯合。我们发现E1 A12 S可以抑制c-Fos激活功能。E1 A突变体的使用表明CBP而不是RB与E1 A的结合对于E1 A介导的抑制是必需的。这些数据支持E1 A通过直接竞争CBP共激活蛋白来调节AP 1活性的模型。
The CBP protein stimulates transcription of cAMP-responsive genes by binding to the phosphorylated activation domain of the CREB transcription factor. Here we show that CBP stimulates transcription of Fos/Jun activity in F9 cells and that this response is mediated, at least partly, via c-Fos, We show that CBP binds c-Fos in a phosphorylation-independent manner in vitro, using a domain distinct from that required to bind CREB. When this CBP domain is linked to the activation domain of VP16 it can stimulate GAL4-Fos activity in vivo. The domain of CBP that binds c-Fos is also used to contact the E1A protein, We therefore asked whether the documented repression of AP1 activity by E1A is due to sequestration of CBP from c-Fos. We show that E1A 12S can repress c-Fos activation functions. The use of E1A mutants indicates that binding of CBP, but not RB, to E1A is essential for E1A-mediated repression. These data support a model whereby E1A can modulate AP1 activity by directly competing for the CBP co-activator protein.