Simpson-Lavy Kobi, Kupiec Martin
The Shmunis School of Biomedicine & Cancer Research, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Biology (Basel). 2023 Jul 14;12(7):1007. doi: 10.3390/biology12071007.
Snf1, the fungal homologue of mammalian AMP-dependent kinase (AMPK), is a key protein kinase coordinating the response of cells to a shortage of glucose. In fungi, the response is to activate respiratory gene expression and metabolism. The major regulation of Snf1 activity has been extensively investigated: In the absence of glucose, it becomes activated by phosphorylation of its threonine at position 210. This modification can be erased by phosphatases when glucose is restored. In the past decade, two additional independent mechanisms of Snf1 regulation have been elucidated. In response to glucose (or, surprisingly, also to DNA damage), Snf1 is SUMOylated by Mms21 at lysine 549. This inactivates Snf1 and leads to Snf1 degradation. More recently, glucose-induced proton export has been found to result in Snf1 inhibition via a polyhistidine tract (13 consecutive histidine residues) at the N-terminus of the Snf1 protein. Interestingly, the polyhistidine tract plays also a central role in the response to iron scarcity. This review will present some of the glucose-sensing mechanisms of , how they interact, and how their interplay results in Snf1 inhibition by three different, and independent, mechanisms.
Snf1是哺乳动物AMP依赖激酶（AMPK）的真菌同源物，是一种关键的蛋白激酶，可协调细胞对葡萄糖短缺的反应。在真菌中，这种反应是激活呼吸基因表达和代谢。Snf1活性的主要调节机制已得到广泛研究：在缺乏葡萄糖的情况下，其第210位苏氨酸的磷酸化使其被激活。当恢复葡萄糖供应时，磷酸酶可以消除这种修饰。在过去十年中，又阐明了另外两种独立的Snf1调节机制。响应葡萄糖（或者令人惊讶的是，也响应DNA损伤），Snf1在赖氨酸549处被Mms21 SUMO化。这使Snf1失活并导致Snf1降解。最近，已发现葡萄糖诱导的质子输出通过Snf1蛋白N端的多聚组氨酸序列（13个连续的组氨酸残基）导致Snf1抑制。有趣的是，多聚组氨酸序列在对铁缺乏的反应中也起着核心作用。本综述将介绍Snf1的一些葡萄糖感应机制、它们如何相互作用，以及它们的相互作用如何通过三种不同且独立的机制导致Snf1抑制。
