ATF-2 CONTAINS A PHOSPHORYLATION-DEPENDENT TRANSCRIPTIONAL ACTIVATION DOMAIN
ATF-2 CONTAINS A PHOSPHORYLATION-DEPENDENT TRANSCRIPTIONAL ACTIVATION DOMAIN
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DOI：
10.1002/j.1460-2075.1995.tb07167.x
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发表时间：
1995-04-18
期刊：
影响因子：
11.4
通讯作者：
JONES, N
中科院分区：
文献类型：
--
作者：
LIVINGSTONE, C;PATEL, G;JONES, N
ATF-2转录因子可介导腺病毒E1a诱导的转录激活。缺失分析表明，ATF-2的N-末端区域是这种反应所必需的。此外，当N-末端与异源DNA结合域融合时，在没有E1a的情况下可以激活转录。然而，在完整的蛋白质中，这个激活结构域被屏蔽了。在这份报告中，我们表明激活所需的N末端残基也是介导E1A刺激所必需的。特别是，第69位和第71位的两个苏氨酸残基是必不可少的。这些残基在体内被磷酸化，在体外可以被MAPK家族的JNK/SAPK亚基有效地磷酸化。ATF-2可以通过N端不同于磷酸化部位的区域与UV诱导的激酶结合，该结合区域对于JNK/SAPK在体外的磷酸化和在体内的转录激活都是必需的。紫外线照射可刺激N-末端的活性，从而刺激导致JNK/SAPK的信号通路。最后，虽然ATF-2与E1A蛋白结合，但这种相互作用并不需要N末端的激活结构域。结果表明，与ATF/CREB DNA结合蛋白家族的其他成员一样，ATF-2受特定信号通路的调控。
The ATF-2 transcription factor can mediate adenovirus E1A-inducibie transcriptional activation. Deletion analysis has indicated that the N-terminal region of ATF-2 is essential for this response. Furthermore, the N-terminus can activate transcription in the absence of E1A when fused to a heterologous DNA binding domain. However, in the intact protein this activation domain is masked. In this report we show that residues in the N-terminus required for activation are also required for mediating E1A stimulation. In particular two threonine residues at positions 69 and 71 are essential. These residues are phosphorylated in vivo and can be efficiently phosphorylated in vitro by the JNK/SAPK subgroup of the MAPK family. ATF-2 can bind to a UV-inducible kinase through a region in the N-terminus that is distinct from the sites of phosphorylation; this binding region is both necessary for phosphorylation by JNK/SAPK in vitro and for transcriptional activation in vivo. The activity of the N-terminus is stimulated by UV irradiation which stimulates the signalling pathway leading to JNK/SAPK. Finally, although ATF-2 binds to the E1A protein, the N-terminal activation domain is not required for this interaction. The results show that ATF-2, like other members of the ATF/CREB family of DNA binding proteins is regulated by specific signalling pathways.