Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant Cells.

Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant Cells.
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DOI:
10.1016/j.tem.2017.07.003
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发表时间:
2017-11
期刊:
Trends in endocrinology and metabolism: TEM
影响因子:
--
通讯作者:
van Leeuwen FN
van Leeuwen FN
中科院分区:
其他
文献类型:
--
作者:
Wortel IMN;van der Meer LT;Kilberg MS;van Leeuwen FN

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激活转录因子4(ATF4)是一种应激诱导的转录因子,在癌细胞中经常上调。ATF4控制着一系列适应性基因的表达,这些基因允许细胞承受一段时间的压力,如缺氧或氨基酸限制。然而,在持续应激条件下,ATF 4促进细胞凋亡的诱导。最近的进展指出了翻译后修饰(PTM)和表观遗传机制在平衡ATF 4的这些促生存和抗生存作用中的作用。我们在这里审查如何PTM和表观遗传修饰剂与ATF 4可能被利用的癌细胞,以科普与肿瘤生长内在相关的细胞应激条件。鉴定调节ATF4介导的转录及其对细胞代谢的影响的机制可能会发现癌症治疗的新靶点。
Activating transcription factor 4 (ATF4) is a stress-induced transcription factor that is frequently upregulated in cancer cells. ATF4 controls the expression of a wide range of adaptive genes that allow cells to endure periods of stress, such as hypoxia or amino acid limitation. However, under persistent stress conditions, ATF4 promotes the induction of apoptosis. Recent advances point to a role for post-translational modifications (PTMs) and epigenetic mechanisms in balancing these pro- and anti-survival effects of ATF4. We review here how PTMs and epigenetic modifiers associated with ATF4 may be exploited by cancer cells to cope with cellular stress conditions that are intrinsically associated with tumor growth. Identification of mechanisms that modulate ATF4-mediated transcription and its effects on cellular metabolism may uncover new targets for cancer treatment.
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