Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells.
Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells.
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DOI：
10.1093/nar/gkn1082
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发表时间：
2009-04
影响因子：
14.9
通讯作者：
Kitajima S
中科院分区：
文献类型：
--
作者：
Miyazaki K;Inoue S;Yamada K;Watanabe M;Liu Q;Watanabe T;Adachi MT;Tanaka Y;Kitajima S
应激反应基因ATF 3在有丝分裂或应激刺激下决定细胞命运方面发挥多效性作用。最近报道了人ATF 3基因的另一个启动子（在本研究中命名为P1），其位于先前报道的P2启动子上游约43.5kb处。我们发现P1启动子在人和小鼠之间高度保守，并且在响应各种刺激时具有功能，而P1启动子主要由血清诱导，P2启动子在响应TGF-β和致癌HRAS时更有效地激活。P1启动子含有多个转录起始位点，不同的5′-UTR显著影响其在胁迫下的翻译。在人前列腺癌和Hodgkin Reed-Sternberg癌细胞中，ATF 3表达升高，P1启动子被组成性激活，其染色质结构被修饰为活性构型。ATF 3基因启动子在转录和翻译水平上的差异使用以及染色质结构的改变可能为表达ATF 3在应激反应和癌症过程中决定细胞命运提供了一种新的机制。
Stress response gene ATF3 plays a pleiotropic role in determining cell fate in response to mitogenic or stress stimuli. An alternate promoter of the human ATF3 gene (designated P1 in this study) has recently been reported, which is located ∼43.5 kb upstream of the previously reported P2 promoter. We showed here that the P1 promoter is highly conserved between human and mouse and is functional in response to various stimuli, whereas the P1 promoter was dominantly induced by serum and the P2 promoter was more efficiently activated in response to TGF-β and oncogenic HRAS. The P1 promoter contains multiple transcriptional start sites, and the different 5′-UTRs markedly affected their translation in response to stress. In human prostate and Hodgkin Reed–Sternberg cancer cells with elevated expression of ATF3, the P1 promoter was constitutively activated and its chromatin structure was modified into active configuration. The differential usage of alternate promoters of the ATF3 gene at both transcriptional and translational level and the modification of chromatin structure may provide a novel mechanism for expressing ATF3 in determining cell fate during stress response and cancer.
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影响因子：
7
作者：
Davuluri, RV;Suzuki, Y;Zhang, MQ
通讯作者：
Zhang, MQ
DOI：
10.1084/jem.20072254
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gilchrist M;Henderson WR Jr;Clark AE;Simmons RM;Ye X;Smith KD;Aderem A
通讯作者：
Aderem A
影响因子：
4.1
作者：
Lu, Dan;Chen, Jingchun;Hai, Tsonwin
通讯作者：
Hai, Tsonwin
影响因子：
7
作者：
Kimura, K;Wakamatsu, A;Sugano, S
通讯作者：
Sugano, S
影响因子：
4.8
作者：
Kawauchi, J;Zhang, C;Kitajima, S
通讯作者：
Kitajima, S