Modulation of thermal induction of hsp70 expression by Ku autoantigen or its individual subunits.
Modulation of thermal induction of hsp70 expression by Ku autoantigen or its individual subunits.
复制标题
Ku 自身抗原或其单个亚基对 hsp70 表达的热诱导调节。
DOI：
10.1128/mcb.16.7.3799
复制
发表时间：
1996
影响因子：
5.3
通讯作者：
Li,GC
中科院分区：
文献类型：
--
作者：
Yang,SH;Nussenzweig,A;Li,L;Kim,D;Ouyang,H;Burgman,P;Li,GC
在此之前，我们提出了一个双重控制机制的调节哺乳动物细胞中的热休克反应：热休克转录因子HSF 1介导的阳性对照和组成型热休克元件结合因子（CHBF）介导的阴性对照。为了研究CHBF在调节热休克反应中的生理作用，我们将CHBF纯化至表观均一性，并显示它与Ku自身抗原相同，Ku自身抗原是由70-kDa（Ku-70）和86-kDa（Ku-80）多肽组成的异源二聚体。为了进一步研究Ku/CHBF在细胞热休克反应中的功能意义，我们建立了稳定和组成型过表达一个或两个亚基的人Ku蛋白的啮齿动物细胞系，并研究了热休克蛋白70和其他热休克蛋白在这些Ku过表达细胞中的热诱导作用。我们表明，表达的人Ku-70和Ku-80亚基联合或Ku-70亚基单独特异性抑制热诱导的热休克蛋白70的表达。相反，单独表达人Ku-80不具有这种效果。其他热休克蛋白在所有的Ku-过表达细胞系的热诱导似乎没有受到显着影响，也不是磷酸化状态或DNA结合能力的HSF 1的影响。这些发现支持了一个模型，其中热休克蛋白70的表达控制的第二个调节因子，除了积极激活的HSF 1。Ku蛋白，特别是Ku-70亚基，参与hsp 70基因表达的调节。
Previously, we proposed a dual control mechanism for the regulation of the heat shock response in mammalian cells: a positive control mediated by the heat shock transcription factor HSF1 and a negative control mediated by the constitutive heat shock element-binding factor (CHBF). To study the physiological role of CHBF in the regulation of heat shock response, we purified CHBF to apparent homogeneity and showed it to be identical to the Ku autoantigen, a heterodimer consisting of 70-kDa (Ku-70) and 86-kDa (Ku-80) polypeptides. To study further the functional significance of Ku/CHBF in the cellular response to heat shock, we established rodent cell lines that stably and constitutively overexpressed one or both subunits of the human Ku protein, and examined the thermal induction of hsp70 and other heat shock proteins in these Ku-overexpressing cells. We show that expression of the human Ku-70 and Ku-80 subunits jointly or of the Ku-70 subunit alone specifically inhibits heat-induced hsp70 expression. Conversely, expression of human Ku-80 alone does not have this effect. Thermal induction of other heat shock proteins in all of the Ku-overexpressing cell lines appears not to be significantly affected, nor is the state of phosphorylation or the DNA-binding ability of HSF1 affected. These findings support a model in which hsp70 expression is controlled by a second regulatory factor in addition to the positive activation of HSF1. The Ku protein, specifically the Ku-70 subunit, is involved in the regulation of hsp70 gene expression.