激活转录因子 (ATF)/cAMP 反应元件结合蛋白 (CREB) 家族代表一大类碱性区亮氨酸拉链 (bZIP) 转录因子 (TF)，具有多种生理功能，例如内质网 (ER) 应激、氨基酸应激、热应激、氧化应激、综合应激反应（ISR），从而诱导细胞存活或凋亡。有趣的是，近年来，ATF 家族越来越多地与自噬和铁死亡相关。因此，ATF 家族对于体内平衡很重要，其失调可能会促进包括癌症在内的疾病进展。目前调节 ATF 家族的治疗方法包括直接调节剂、上游调节剂、翻译后修饰 (PTM) 调节剂。本文综述了ATF/CREB家族的结构域和翻译后修饰特征，并全面探讨了其分子调控机制。在此基础上，对它们影响各类癌细胞增殖、转移和耐药的通路进行了梳理和讨论。我们系统总结了现有ATF家族调节剂的治疗应用现状，最后展望了通过调节ATF家族调节剂治疗肿瘤的临床应用前景。版权所有©2024 The Author(s)。由爱思唯尔有限公司出版。保留所有权利。

The activating transcription factor (ATF)/ cAMP-response element binding protein (CREB) family represents a large group of basic zone leucine zip (bZIP) transcription factors (TFs) with a variety of physiological functions, such as endoplasmic reticulum (ER) stress, amino acid stress, heat stress, oxidative stress, integrated stress response (ISR) and thus inducing cell survival or apoptosis. Interestingly, ATF family has been increasingly implicated in autophagy and ferroptosis in recent years. Thus, the ATF family is important for homeostasis and its dysregulation may promote disease progression including cancer. Current therapeutic approaches to modulate the ATF family include direct modulators, upstream modulators, post-translational modifications (PTMs) modulators. This review summarizes the structural domain and the PTMs feature of the ATF/CREB family and comprehensively explores the molecular regulatory mechanisms. On this basis, their pathways affecting proliferation, metastasis, and drug resistance in various types of cancer cells are sorted out and discussed. We then systematically summarize the status of the therapeutic applications of existing ATF family modulators and finally look forward to the future prospect of clinical applications in the treatment of tumors by modulating the ATF family.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.