Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, Technical University of Lisbon, Lisboa, Portugal.
OMICS. 2010 Oct;14(5):587-601. doi: 10.1089/omi.2010.0048.
The alterations occurring in yeast genomic expression during early response to acetic acid and the involvement of the transcription factor Haa1p in this transcriptional reprogramming are described in this study. Haa1p was found to regulate, directly or indirectly, the transcription of approximately 80% of the acetic acid-activated genes, suggesting that Haa1p is the main player in the control of yeast response to this weak acid. The genes identified in this work as being activated in response to acetic acid in a Haa1p-dependent manner include protein kinases, multidrug resistance transporters, proteins involved in lipid metabolism, in nucleic acid processing, and proteins of unknown function. Among these genes, the expression of SAP30 and HRK1 provided the strongest protective effect toward acetic acid. SAP30 encode a subunit of a histone deacetylase complex and HRK1 encode a protein kinase belonging to a family of protein kinases dedicated to the regulation of plasma membrane transporters activity. The deletion of the HRK1 gene was found to lead to the increase of the accumulation of labeled acetic acid into acid-stressed yeast cells, suggesting that the role of both HAA1 and HRK1 in providing protection against acetic acid is, at least partially, related with their involvement in the reduction of intracellular acetate concentration.
本研究描述了酵母基因组表达在早期响应乙酸时发生的变化，以及转录因子 Haa1p 在这种转录重编程中的作用。研究发现，Haa1p 直接或间接调节约 80%的乙酸激活基因的转录，这表明 Haa1p 是控制酵母对这种弱酸反应的主要因素。本研究中确定的以 Haa1p 依赖性方式响应乙酸而激活的基因包括蛋白激酶、多药耐药转运蛋白、参与脂质代谢、核酸加工以及功能未知的蛋白。在这些基因中，SAP30 和 HRK1 的表达对乙酸提供了最强的保护作用。SAP30 编码组蛋白去乙酰化酶复合物的一个亚基，而 HRK1 编码属于蛋白激酶家族的一种蛋白激酶，该家族蛋白激酶专门用于调节质膜转运蛋白的活性。发现删除 HRK1 基因会导致标记乙酸在酸胁迫酵母细胞中的积累增加，这表明 HAA1 和 HRK1 两者在提供对乙酸的保护作用中至少部分与它们参与降低细胞内乙酸浓度有关。
