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) 是一种应激诱导的转录因子，在癌细胞中经常上调。ATF4 控制多种适应性基因的表达，这些基因使细胞能够承受压力，例如缺氧或氨基酸限制。然而，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 的这些促存活和抗存活作用方面的作用。我们在这里回顾了癌细胞如何利用与 ATF4 相关的 PTM 和表观遗传修饰符来应对与肿瘤生长内在相关的细胞应激条件。