Zelin Elena, Freeman Brian C
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, USA.
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, USA.
J Mol Biol. 2015 Apr 10;427(7):1644-54. doi: 10.1016/j.jmb.2015.02.010. Epub 2015 Feb 15.
Heat shock factor 1 (HSF1) is critical for defending cells from both acute and chronic stresses. In aging cells, the DNA binding activity of HSF1 deteriorates correlating with the onset of pathological events including neurodegeneration and heart disease. We find that DNA binding by HSF1 is controlled by lysine deacetylases with HDAC7, HDAC9, and SIRT1 distinctly increasing the magnitude and length of a heat shock response (HSR). In contrast, HDAC1 inhibits HSF1 in a deacetylase-independent manner. In aging cells, the levels of HDAC1 are elevated and the HSR is impaired, yet reduction of HDAC1 in aged cells restores the HSR. Our results provide a mechanistic basis for the age-associated regulation of the HSR. Besides HSF1, the deacetylases differentially modulate the activities of unrelated DNA binding proteins. Taken together, our data further support the model that lysine deacetylases are selective regulators of DNA binding proteins.
热休克因子1（HSF1）对于保护细胞免受急性和慢性应激至关重要。在衰老细胞中，HSF1的DNA结合活性会随着包括神经退行性变和心脏病在内的病理事件的发生而恶化。我们发现，HSF1的DNA结合受赖氨酸脱乙酰酶控制，其中HDAC7、HDAC9和SIRT1显著增加热休克反应（HSR）的幅度和时长。相反，HDAC1以一种不依赖脱乙酰酶的方式抑制HSF1。在衰老细胞中，HDAC1的水平升高且HSR受损，但降低衰老细胞中HDAC1的水平可恢复HSR。我们的结果为HSR的年龄相关调控提供了一个机制基础。除了HSF1，这些脱乙酰酶还以不同方式调节无关DNA结合蛋白的活性。综上所述，我们的数据进一步支持了赖氨酸脱乙酰酶是DNA结合蛋白的选择性调节因子这一模型。
