营养物质和能量缺乏时，细胞一方面通过抑制合成代谢，下调细胞内耗能过程；一方面通过启动自噬等细胞内分解过程以获取能量和营养，维持细胞稳态。饥饿应激时，细胞协调合成代谢和分解代谢过程的分子信号机制尚有众多科学问题有待解决。前期工作中我们发现，细胞饥饿时自噬相关蛋白ATG4B会从细胞质易位至细胞核中，且该易位事件与自噬发生无关；在细胞中直接表达定位细胞核的ATG4B突变体，能显著抑制细胞DNA合成，提示ATG4B除了调控自噬过程，还能通过移位细胞核参与调控细胞DNA合成。本项目将在前期研究结果基础上，进一步深入研究核内ATG4B的功能；解析ATG4B的入核调控过程；通过鉴定ATG4B的核内相互作用蛋白，揭示核内ATG4B抑制细胞DNA合成的分子机制。研究结果将不仅揭示ATG4B蛋白的新功能，也将阐明饥饿应激时，细胞抑制DNA合成的新机制，拓宽我们对应激状态下细胞协调合成代谢和分解代谢过程的认识。

During nutrient and energy deprivation, cell will inhibit the anabolism to reduce the consumption of energy and nutrient. At the same time, many catabolic processes, such as autophagy, will be enhanced to serves as an alternative energy and nutrient source for cells survival. However, it is still elusive how cells coordinate the anabolism and catabolism during starvation. In our previous works, we found that during starvation, ATG4B will translocate from cytoplasm to nucleus through a pathway independent of autophagy. Expressing of a nuclear-localized ATG4B mutation can dramatically inhibit the cellular DNA synthesis. These data suggest that ATG4B regulates not only autophagy but also cellular DNA synthesis during starvation. In this study, we will further investigate the regulation and function of ATG4B nuclear-localization, identify the signal pathway and interaction protein of nuclear ATG4B. This study will dissect the molecular mechanism of DNA synthesis inhibition by nuclear ATG4B, and further unravel the coordination between the anabolism and catabolism during starvation.