Casein Kinase I Isoform Hrr25 Is a Negative Regulator of Haa1 in the Weak Acid Stress Response Pathway in Saccharomyces cerevisiae
Casein Kinase I Isoform Hrr25 Is a Negative Regulator of Haa1 in the Weak Acid Stress Response Pathway in Saccharomyces cerevisiae
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DOI：
10.1128/aem.00672-17
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发表时间：
2017-07-01
影响因子：
4.4
通讯作者：
Liu, Zhengchang
中科院分区：
文献类型：
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作者：
Collins, Morgan E.;Black, Joshua J.;Liu, Zhengchang
Haa 1是一种转录因子，通过激活多种基因的表达来使酿酒酵母细胞适应弱有机酸胁迫。这些基因中的许多编码膜蛋白，如TPO 2和YRO 2。Haa 1如何被弱酸激活尚不清楚。在这里，我们表明，酪蛋白激酶I亚型Hrr 25是一个重要的负调节Haa 1。已知Haa 1是多重磷酸化的。我们发现HRR 25突变导致Haa 1磷酸化减少和Haa 1靶基因表达增加，并且Hrr 25与Haa 1相互作用。其他三个酪蛋白激酶I亚型，Yck 1，Yck 2和Yck 3，似乎没有发挥关键作用Haa 1的调节。Hrr 25具有200个残基的C-末端区域，包括富含脯氨酸和谷氨酰胺的结构域。我们的数据表明，Hrr 25的C-末端区域是正常抑制Haa 1靶基因TPO 2和YRO 2的表达所必需的，并且对细胞生长很重要，但对细胞形态发生不是必需的。我们建议，Hrr 25是一个重要的调节细胞适应弱酸stress.IMPORTANCE通过磷酸化抑制Haa 1我们的研究揭示了酪蛋白激酶I蛋白Hrr 25是一个负调节Haa 1，转录因子介导的细胞反应引起的弱酸应力。许多研究都集中在Haa 1的靶基因及其在弱酸胁迫反应中的作用，但关于Haa 1的调控机制的报道很少。弱酸，如乙酸，长期以来一直用于食品防腐，通过减缓真菌物种的生长，包括S。啤酒。在生物燃料工业中，木质纤维素水解产物中的乙酸限制了乙醇的生产，这是不期望的。通过了解Haa 1是如何调节的，我们可以在食品科学领域取得进展，以更好地保存食品和工程抗乙酸菌株，从而提高生物燃料行业的生产力。
Haa1 is a transcription factor that adapts Saccharomyces cerevisiae cells to weak organic acid stresses by activating the expression of various genes. Many of these genes encode membrane proteins, such as TPO2 and YRO2. How Haa1 is activated by weak acids is not clear. Here, we show that casein kinase I isoform Hrr25 is an important negative regulator of Haa1. Haa1 is known to be multiply phosphorylated. We found that mutations in HRR25 lead to reduced Haa1 phosphorylation and increased expression of Haa1 target genes and that Hrr25 interacts with Haa1. The other three casein kinase I isoforms, Yck1, Yck2, and Yck3, do not seem to play critical roles in Haa1 regulation. Hrr25 has a 200-residue C-terminal region, including a proline- and glutamine-rich domain. Our data suggest that the C-terminal region of Hrr25 is required for normal inhibition of expression of Haa1 target genes TPO2 and YRO2 and is important for cell growth but is not required for cell morphogenesis. We propose that Hrr25 is an important regulator of cellular adaptation to weak acid stress by inhibiting Haa1 through phosphorylation.IMPORTANCE Our study has revealed the casein kinase I protein Hrr25 to be a negative regulator of Haa1, a transcription factor mediating the cellular response to stresses caused by weak acids. Many studies have focused on the target genes of Haa1 and their roles in weak acid stress responses, but little has been reported on the regulatory mechanism of Haa1. Weak acids, such as acetic acid, have long been used for food preservation by slowing down the growth of fungal species, including S. cerevisiae. In the biofuel industry, acetic acid in the lignocellulosic hydrolysates limits the production of ethanol, which is undesirable. By understanding how Haa1 is regulated, we can make advances in the field of food sciences to better preserve food and engineer acetic acid-resistant strains that will increase productivity in the biofuel industry.