Activating transcription factor 4
Activating transcription factor 4
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DOI：
10.1016/j.biocel.2007.01.020
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Harris, Adrian L.
中科院分区：
文献类型：
--
作者：
Ameri, Kurosh;Harris, Adrian L.
激活转录因子4(ATF4)属于碱性亮氨酸拉链(BZip)转录因子的ATF/CREB(激活转录因子/环AMP反应元件结合蛋白)家族，具有共同的结合位点cAMP反应元件(CRE)。ATF4有许多二聚合作伙伴。ATF4是由包括缺氧/缺氧、内质网应激、氨基酸剥夺和氧化应激等应激信号诱导的。ATF4的表达受转录调控，翻译上通过eIF2α磷酸化的PERK途径调节，翻译后通过磷酸化调节，目的是使ATF4降解到蛋白酶体。ATF4调控氧化应激、氨基酸合成、分化、转移和血管生成等相关基因的表达。转基因研究表明，ATF4参与了造血、晶状体和骨骼发育、生育、增殖、分化和长期记忆。ATF4在癌症中表达上调。由于ATF4是由肿瘤微环境因素诱导的，并调节与癌症进展相关的过程，因此它可能成为癌症的潜在治疗靶点。(C)2007年由爱思唯尔有限公司出版。
Activating transcription factor 4 (ATF4) belongs to the ATF/CREB (activating transcription factor/cyclic AMP response element binding protein) family of basic region-leucine zipper (bZip) transcription factors, which have the consensus binding site cAMP responsive element (CRE). ATF4 has numerous dimerization partners. ATF4 is induced by stress signals including anoxia/hypoxia, endoplasmic reticulum stress, amino acid deprivation, and oxidative stress. ATF4 expression is regulated transcriptionally, translationally via the PERK pathway of eIF2 alpha phosphorylation, and posttranslationally by phosphorylation, which targets ATF4 to proteasomal degradation. ATF4 regulates the expression of genes involved in oxidative stress, amino acid synthesis, differentiation, metastasis and angiogenesis. Transgenic studies have demonstrated ATF4 to be involved in hematopoiesis, lens and skeletal development, fertility, proliferation, differentiation, and long-term memory. ATF4 expression is upregulated in cancer. Since ATF4 is induced by tumour microenvironmental factors, and regulates processes relevant to cancer progression, it might serve as a potential therapeutic target in cancer. (C) 2007 Published by Elsevier Ltd.