Whi2: a new player in amino acid sensing.
Whi2: a new player in amino acid sensing.
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Whi2：氨基酸传感领域的新玩家。
DOI：
10.1007/s00294-018-00929-9
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发表时间：
2019
期刊：
影响因子：
2.5
通讯作者：
Hardwick,JMarie
中科院分区：
文献类型：
--
作者：
Teng,Xinchen;Hardwick,JMarie
人类、酵母和细菌细胞的一个关键功能是感知和响应可用营养物质，如葡萄糖和氨基酸。细胞还必须检测到营养水平的下降，通过抑制细胞生长和激活自噬来为饥饿条件做好充分准备。进化上保守的蛋白质复合体TORC1调节这些细胞对营养物质的反应，特别是对氨基酸的可获得性。最近，我们发现酵母Whi2(酿酒酵母)和人类对应的KCTD11，具有保守的BTB结构域，在低氨基酸条件下需要抑制TORC1的活性。使用酵母，这些机制更容易被剖析。出人意料的是，WHI2抑制TORC1的活性不依赖于众所周知的SEACIT-GTR途径，类似于哺乳动物的GATOR1-RAG途径。相反，Whi2需要质膜相关的磷酸酶Psr1和Psr2，这两种酶已知与Whi2结合，尽管它们的作用尚不清楚。YeastWHI2此前被报道参与调控几个基本的细胞过程，包括细胞周期停滞、一般应激反应、Ras-cAMP-PKA途径、自噬和有丝分裂吞噬，并在酵母基因敲除样本和基因组进化研究中频繁突变。这些观察结果中的大多数可能是由于Whi2抑制TORC1的能力所解释的。因此，了解酵母Whi2的功能将有助于更深入地了解与疾病相关的KCTD家族蛋白以及植物和人类真菌感染的发病机制。
A critical function of human, yeast, and bacterial cells is the ability to sense and respond to available nutrients such as glucose and amino acids. Cells must also detect declining nutrient levels to adequately prepare for starvation conditions by inhibiting cell growth and activating autophagy. The evolutionarily conserved protein complex TORC1 regulates these cellular responses to nutrients, and in particular to amino acid availability. Recently, we found that yeast Whi2 (Saccharomyces cerevisiae) and a human counterpart, KCTD11, that shares a conserved BTB structural domain, are required to suppress TORC1 activity under low amino acid conditions. Using yeast, the mechanisms were more readily dissected. Unexpectedly, Whi2 suppresses TORC1 activity independently of the well-known SEACIT–GTR pathway, analogous to the GATOR1–RAG pathway in mammals. Instead, Whi2 requires the plasma membrane-associated phosphatases Psr1 and Psr2, which were known to bind Whi2, although their role was unknown. YeastWHI2was previously reported to be involved in regulating several fundamental cellular processes including cell cycle arrest, general stress responses, the Ras–cAMP–PKA pathway, autophagy, and mitophagy, and to be frequently mutated in the yeast knockout collections and in genome evolution studies. Most of these observations are likely explained by the ability of Whi2 to inhibit TORC1. Thus, understanding the function of yeast Whi2 will provide deeper insights into the disease-related KCTD family proteins and the pathogenesis of plant and human fungal infections.