Simon Hans-Uwe, Friis Robert, Tait Stephen W G, Ryan Kevin M
Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland.
Cancer Research U.K. Beatson Institute, Glasgow G61 1BD, U.K.
Sci Signal. 2017 Feb 28;10(468):eaag2791. doi: 10.1126/scisignal.aag2791.
Macroautophagy is a process in which cytoplasmic components, including whole organelles, are degraded within lysosomes. Basally, this process is essential for homeostasis and is constitutively functional in most cells, but it can also be implemented as part of stress responses. We discuss findings showing that autophagy proteins can modulate and amplify the activities of transcription factors involved in stress responses, such as those in the p53, FOXO, MiT/TFE, Nrf2, and NFκB/Rel families. Thus, transcription factors not only amplify stress responses and autophagy but are also subject to retrograde regulation by autophagy-related proteins. Physical interactions with autophagy-related proteins, competition for activating intermediates, and "signalphagy," which is the role autophagy plays in the degradation of specific signaling proteins, together provide powerful tools for implementing negative feedback or positive feed-forward loops on the transcription factors that regulate autophagy. We present examples illustrating how this network interacts to regulate metabolic and physiologic responses.
巨自噬是一个细胞质成分（包括整个细胞器）在溶酶体内被降解的过程。在基础状态下，这个过程对于体内平衡至关重要，并且在大多数细胞中具有组成性功能，但它也可以作为应激反应的一部分被激活。我们讨论的研究结果表明，自噬蛋白可以调节和放大参与应激反应的转录因子的活性，例如p53、FOXO、MiT/TFE、Nrf2和NFκB/Rel家族中的转录因子。因此，转录因子不仅放大应激反应和自噬，还受到自噬相关蛋白的逆向调节。与自噬相关蛋白的物理相互作用、对激活中间体的竞争以及“信号自噬”（即自噬在特定信号蛋白降解中所起的作用），共同为在调节自噬的转录因子上实施负反馈或正前馈环提供了有力工具。我们给出了一些例子来说明这个网络如何相互作用以调节代谢和生理反应。
