Modification of Phosphorylation Sites in the Yeast Lysine Methyltransferase Set5 Exerts Influences on the Mitogen-Activated Protein Kinase Hog1 under Prolonged Acetic Acid Stress.
Modification of Phosphorylation Sites in the Yeast Lysine Methyltransferase Set5 Exerts Influences on the Mitogen-Activated Protein Kinase Hog1 under Prolonged Acetic Acid Stress.
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DOI：
10.1128/spectrum.03011-22
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发表时间：
2023-03-28
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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作者：
芽殖酵母酿酒酵母对乙酸毒性的反应在木质纤维素生物质的生物炼制和食品保存中具有广泛的意义。我们前期的研究表明，Set 5，酵母赖氨酸甲基转移酶和组蛋白H4甲基转移酶，参与了乙酸胁迫耐受。然而，Set 5如何与已知的压力信号网络发挥作用和相互作用仍然是个谜。在这里，我们发现，升高磷酸化的Set 5在乙酸胁迫是伴随着增强表达的丝裂原活化蛋白激酶（MAPK）Hog 1。进一步的实验发现，Set 5的拟磷酸化突变赋予酵母细胞改善的生长和发酵性能，并改变了特定应激反应基因的转录。有趣的是，Set 5被发现结合HOG 1的编码区并调节其转录，沿着Hog 1的表达和磷酸化增加。Set 5和Hog 1之间的蛋白质-蛋白质相互作用也被揭示。此外，Set 5磷酸化位点的修饰被证明可以调节活性氧（ROS）的积累，这是已知的影响酵母乙酸胁迫耐受性。这项研究的结果表明，Set 5可能与中央激酶Hog 1一起协调细胞的生长和代谢，以应对压力。重要信息Hog 1是哺乳动物中p38 MAPK的酵母同源物，在真核生物中保守，在胁迫耐受性、真菌发病机制和疾病治疗中起关键作用。在这里，我们提供的证据表明，修改Set 5磷酸化位点调节Hog 1的表达和磷酸化，这扩大了目前的知识Hog 1应激信号网络的上游调控。Set 5及其同源蛋白存在于人类和各种真核生物中。在这项研究中，Set 5磷酸化位点修饰的新发现的作用有利于深入了解真核生物应激信号传导，以及人类疾病的治疗。
Responses to acetic acid toxicity in the budding yeast Saccharomyces cerevisiae have widespread implications in the biorefinery of lignocellulosic biomass and food preservation. Our previous studies revealed that Set5, the yeast lysine methyltransferase and histone H4 methyltransferase, was involved in acetic acid stress tolerance. However, it is still mysterious how Set5 functions and interacts with the known stress signaling network. Here, we revealed that elevated phosphorylation of Set5 during acetic acid stress is accompanied by enhanced expression of the mitogen-activated protein kinase (MAPK) Hog1. Further experiments uncovered that the phosphomimetic mutation of Set5 endowed yeast cells with improved growth and fermentation performance and altered transcription of specific stress-responsive genes. Intriguingly, Set5 was found to bind the coding region of HOG1 and regulate its transcription, along with increased expression and phosphorylation of Hog1. A protein-protein interaction between Set5 and Hog1 was also revealed. In addition, modification of Set5 phosphosites was shown to regulate reactive oxygen species (ROS) accumulation, which is known to affect yeast acetic acid stress tolerance. The findings in this study imply that Set5 may function together with the central kinase Hog1 to coordinate cell growth and metabolism in response to stress. IMPORTANCE Hog1 is the yeast homolog of p38 MAPK in mammals that is conserved across eukaryotes, and it plays crucial roles in stress tolerance, fungal pathogenesis, and disease treatments. Here, we provide evidence that modification of Set5 phosphorylation sites regulates the expression and phosphorylation of Hog1, which expands current knowledge on upstream regulation of the Hog1 stress signaling network. Set5 and its homologous proteins are present in humans and various eukaryotes. The newly identified effects of Set5 phosphorylation site modifications in this study benefit an in-depth understanding of eukaryotic stress signaling, as well as the treatment of human diseases.
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影响因子：
7
作者：
Beyer, A;Hollunder, J;Wilhelm, T
通讯作者：
Wilhelm, T
酿酒酵母中糠醛和乙酸的转录组变化
影响因子：
5
作者：
Li, Bing-Zhi;Yuan, Ying-Jin
通讯作者：
Yuan, Ying-Jin
影响因子：
64.8
作者：
Mazur, Pawel K.;Reynoird, Nicolas;Khatri, Purvesh;Jansen, Pascal W. T. C.;Wilkinson, Alex W.;Liu, Shichong;Barbash, Olena;Van Aller, Glenn S.;Huddleston, Michael;Dhanak, Dashyant;Tummino, Peter J.;Kruger, Ryan G.;Garcia, Benjamin A.;Butte, Atul J.;Vermeulen, Michiel;Sage, Julien;Gozani, Or
通讯作者：
Gozani, Or
影响因子：
14.9
作者：
He, Ming-Hong;Liu, Jia-Cheng;Zhou, Jin-Qiu
通讯作者：
Zhou, Jin-Qiu
DOI：
10.1002/yea.3651
发表时间：
2021-07
期刊：
Yeast (Chichester, England)
影响因子：
--
作者：
Guaragnella N;Bettiga M
通讯作者：
Bettiga M