Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160062, India.
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160062, India.
Biochim Biophys Acta Mol Cell Res. 2022 May;1869(5):119238. doi: 10.1016/j.bbamcr.2022.119238. Epub 2022 Feb 10.
The aim of this work was to identify elements of adaptive regulatory mechanism for basal level of yeast histone deacetylase Sir2. Heat shock response (HSR) was altered in the absence of the NAD-dependent glycerol 3-phosphate dehydrogenase (Gpd1). Increase in HSR was lower in ΔGpd1 cells than wild-type cells. An inverse correlation existed between Gpd1 and Sir2; Sir2-deleted cells showed higher expression of Gpd1 while deletion of Gpd1 led to higher expression of Sir2. In the absence of Gpd1, basal activity of Sir2 promoter was higher and was increased further upon heat shock, suggesting higher Sir2 levels. No interaction between Gpd1 and Sir2 was detected without or with heat shock using immunoprecipitation. The results show that Gpd1 regulates HSR in yeast cells and likely blocks its uncontrolled activation. As uncontrolled stress adversely affects the cellular adaptive response, Gpd1 may be a component of the cell's catalogue to ensure a balanced response to unmitigated thermal stress.
本工作旨在鉴定酵母组蛋白去乙酰化酶 Sir2 基础水平的适应性调节机制的组成部分。在缺乏 NAD 依赖性甘油-3-磷酸脱氢酶 (Gpd1) 的情况下，热激反应 (HSR) 发生改变。与野生型细胞相比，ΔGpd1 细胞中的 HSR 增加较低。Gpd1 与 Sir2 呈负相关；Sir2 缺失细胞中 Gpd1 的表达更高，而 Gpd1 的缺失导致 Sir2 的表达更高。在缺乏 Gpd1 的情况下，Sir2 启动子的基础活性更高，热激后进一步增加，表明 Sir2 水平更高。使用免疫沉淀法，无论是否存在热激，都未检测到 Gpd1 和 Sir2 之间的相互作用。结果表明，Gpd1 调节酵母细胞中的 HSR，并可能阻止其不受控制的激活。由于不受控制的应激会对细胞的适应性反应产生不利影响，因此 Gpd1 可能是细胞目录的一个组成部分，以确保对未缓解的热应激做出平衡的反应。
