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)

被引:103
作者
Liang, GS
Hai, T
机构
[1] OHIO STATE UNIV, BIOCHEM PROGRAM, COLUMBUS, OH 43210 USA
[2] OHIO STATE UNIV, DEPT BIOCHEM MED, COLUMBUS, OH 43210 USA
[3] OHIO STATE UNIV, NEUROBIOTECHNOL CTR, COLUMBUS, OH 43210 USA
关键词
D O I
10.1074/jbc.272.38.24088
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页码:24088 / 24095
页数:8
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