靶向替换小鼠 HSF1 丝氨酸 303/307 位的磷酸化氨基酸为丙氨酸可增加细胞增殖和耐药性。
Targeted Replacement of HSF1 Phosphorylation Sites at S303/S307 with Alanine Residues in Mice Increases Cell Proliferation and Drug Resistance.
机构信息
Molecular Chaperone Biology, Medical College of Georgia, Augusta, GA, USA.
Georgia Cancer Center, Augusta University, Augusta, GA, USA.
出版信息
Methods Mol Biol. 2023;2693:81-94. doi: 10.1007/978-1-0716-3342-7_7.
Mammalian heat shock factor HSF1 transcriptional activity is controlled by a multitude of phosphorylations that occur under physiological conditions or following exposure of cells to a variety of stresses. One set of HSF1 phosphorylation is on serine 303 and serine 307 (S303/S307). These HSF1 phosphorylation sites are known to repress its transcriptional activity. Here, we describe a knock-in mouse model where these two serine residues were replaced by alanine residues and have determined the impact of these mutations on cellular proliferation and drug resistance. Our previous study using this mouse model indicated the susceptibility of the mutant mice to become obese with age due to an increase in basal levels of heat shock proteins (HSPs) and chronic inflammation. Since HSF1 transcriptional activity is increased in many tumor types, this mouse model may be a useful tool for studies related to cellular transformation and cancer.
哺乳动物热休克因子 HSF1 的转录活性受到多种磷酸化的调控，这些磷酸化作用在生理条件下或细胞暴露于各种应激时发生。一组 HSF1 磷酸化作用发生在丝氨酸 303 和丝氨酸 307（S303/S307）。这些 HSF1 磷酸化位点已知会抑制其转录活性。在这里，我们描述了一种敲入小鼠模型，其中这两个丝氨酸残基被丙氨酸残基取代，并确定了这些突变对细胞增殖和耐药性的影响。我们之前使用该小鼠模型的研究表明，由于基础水平的热休克蛋白（HSPs）和慢性炎症增加，突变小鼠易随着年龄增长而肥胖。由于 HSF1 的转录活性在许多肿瘤类型中增加，因此这种小鼠模型可能是研究细胞转化和癌症相关的有用工具。
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