Characterization of human activating transcription factor 4, a transcriptional activator that interacts with multiple domains of cAMP-responsive element-binding protein (CREB)-binding protein (CBP)
Characterization of human activating transcription factor 4, a transcriptional activator that interacts with multiple domains of cAMP-responsive element-binding protein (CREB)-binding protein (CBP)
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DOI：
10.1074/jbc.272.38.24088
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发表时间：
1997-09-19
影响因子：
4.8
通讯作者：
Hai, T
中科院分区：
文献类型：
--
作者：
Liang, GS;Hai, T
我们证明，人激活转录因子4（hATF 4），转录因子激活因子/cAMP反应元件结合蛋白（ATF/CREB）家族的成员，是一个有效的转录激活因子在哺乳动物细胞和酵母。hATF 4的N-末端113个氨基酸有效地激活转录，并且出乎意料地，hATF 4的C-末端bZip DNA结合结构域也激活转录，尽管很弱。我们的研究结果表明，hATF 4与几个一般的转录因子：TATA结合蛋白，TFIIB，和TFIIF的RAP 30亚基相互作用。此外，hATF 4与共激活因子CREB结合蛋白（CBP）在四个区域相互作用：1）KIX结构域，2）包含第三锌指和E1 A相互作用结构域的区域，3）包含p160/SRC-1相互作用结构域的C-末端区域，以及4）最近鉴定的组蛋白乙酰转移酶结构域。有趣的是，hATF 4的N-末端和C-末端区域都与上述通用转录因子和CBP相互作用，为它们激活转录的能力提供了机制解释。与其作为共激活因子的作用一致，CBP增强了hATF 4激活转录的能力。讨论了hATF 4与多种因素相互作用的潜在意义。
We demonstrate that human activating transcription factor 4 (hATF4), a member of the activating transcription factor/cAMP-responsive element-binding protein (ATF/CREB) family of transcription factors, is a potent transcriptional activator in both mammalian cells and yeast. The N-terminal 113 amino acids of hATF4 activate transcription efficiently, and unexpectedly, the C-terminal bZip DNA binding domain of hATF4 also activates transcription, albeit weakly. Our results indicate that hATF4 interacts with several general transcription factors: TATA-binding protein, TFIIB, and the RAP30 subunit of TFIIF. In addition, hATF4 interacts with the coactivator CREB-binding protein (CBP) at four regions: 1) the KIX domain, 2) a region that contains the third zinc finger and the E1A-interacting domain, 3) a C-terminal region that contains the p160/SRC-1-interacting domain, and 4) the recently identified histone acetyltransferase domain. Interestingly, both the N-terminal and C-terminal regions of hATF4 interact with the above general transcription factors and CBP, providing a mechanistic explanation for their ability to activate transcription. Consistent, with its role as a coactivator, CBP potentiates the ability of hATF4 to activate transcription. The potential significance of the interaction between hATF4 and multiple factors is discussed.