Whi2 signals low leucine availability to halt yeast growth and cell death.
Whi2 signals low leucine availability to halt yeast growth and cell death.
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DOI：
10.1093/femsyr/foy095
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发表时间：
2018-08
影响因子：
3.2
通讯作者：
Xinchen Teng;Xinchen Teng;Xinchen Teng;E. Yau;Cierra N. Sing;J. M. Hardwick;J. M. Hardwick
中科院分区：
文献类型：
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作者：
Xinchen Teng;Xinchen Teng;Xinchen Teng;E. Yau;Cierra N. Sing;J. M. Hardwick;J. M. Hardwick
细胞对环境的要求进行了精细的调整。氨基酸的可用性被迅速感知，使细胞能够调整分子过程，并相应地实施短期或长期的代谢转变。大多数单个氨基酸的水平如何被感知并随后发出信号以告知细胞其营养状态在很大程度上是未知的。我们意外地观察到特定氨基酸水平的微小变化可以对酵母细胞生长产生深远的影响，从而将酵母Whi2鉴定为低氨基酸中细胞生长的负调节剂。虽然Whi2最初被认为是真菌特异性的，但Whi2似乎共享在编码KCTD（钾通道四聚化结构域）蛋白家族的25个基本上未表征的人类基因家族中发现的保守结构域。从酵母Whi2中获得的见解可能会揭示人类KCTD，其中许多已经被证明在突变时会导致疾病。在这里，我们报告了新的证据表明，Whi2响应于介质中的特定氨基酸，特别是低亮氨酸水平。我们还讨论了已知的途径的氨基酸信号和潜在的调控点Whi2在酵母和哺乳动物的营养信号。
Cells are exquisitely tuned to environmental ques. Amino acid availability is rapidly sensed, allowing cells to adjust molecular processes and implement short or long-term metabolic shifts accordingly. How levels of most individual amino acids may be sensed and subsequently signaled to inform cells of their nutrient status is largely unknown. We made the unexpected observation that small changes in the levels of specific amino acids can have a profound effect on yeast cell growth, leading to the identification of yeast Whi2 as a negative regulator of cell growth in low amino acids. Although Whi2 was originally thought to be fungi-specific, Whi2 appears to share a conserved structural domain found in a family of 25 largely uncharacterized human genes encoding the KCTD (potassium channel tetramerization domain) protein family. Insights gained from yeast Whi2 are likely to be revealing about human KCTDs, many of which have been implicated or demonstrated to cause disease when mutated. Here we report new evidence that Whi2 responds to specific amino acids in the medium, particularly low leucine levels. We also discuss the known pathways of amino acid signaling and potential points of regulation by Whi2 in nutrient signaling in yeast and mammals.