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.

中文翻译：

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生存的压力：正常和恶性细胞中ATF4介导的应激反应的调节。

激活转录因子4（ATF4）是一种应力诱导的转录因子，在癌细胞中经常被上调。ATF4控制着广泛的适应性基因的表达，这些基因允许细胞忍受压力，例如缺氧或氨基酸限制。但是，在持续的应激条件下，ATF4促进细胞凋亡的诱导。最近的进展表明，翻译后修饰（PTM）和表观遗传机制在平衡ATF4的这些促生存和抗生存作用方面发挥了作用。我们在这里回顾了癌细胞可能如何利用与ATF4相关的PTM和表观遗传修饰剂来应对与肿瘤生长内在相关的细胞应激状况。