Disruption of the HSF3 gene results in the severe reduction of heat shock gene expression and loss of thermotolerance
Disruption of the HSF3 gene results in the severe reduction of heat shock gene expression and loss of thermotolerance
复制标题
DOI：
10.1093/emboj/17.6.1750
复制
发表时间：
1998-03
期刊：
影响因子：
--
通讯作者：
M. Tanabe;Yoshinori Kawazoe;S. Takeda;R. Morimoto;K. Nagata;A. Nakai
中科院分区：
文献类型：
--
作者：
M. Tanabe;Yoshinori Kawazoe;S. Takeda;R. Morimoto;K. Nagata;A. Nakai
脊椎动物基因组编码热休克因子（HSFs 1-4）家族，其中HSF 1和HSF 3的DNA结合和转录活性在热休克时被激活。HSF 1具有经典HSF的性质，并且在暴露于热休克和其他应激条件下时表现出DNA结合和转录活性的快速活化，而HSF 3通常在较高温度下活化，并且具有明显的延迟动力学。为了解决HSF 3在热休克反应中的作用，通过在禽类淋巴细胞系中通过体细胞重组破坏常驻基因来构建缺乏HSF 3基因的空细胞。缺乏HSF 3，但表达正常水平的HSF 1，表现出热休克反应的严重减少，测量诱导表达的热休克基因，并没有表现出耐热性。在中等热休克温度下，其中HSF 1在野生型细胞中寡聚成活性三聚体，HSF 1在HSF 3无效细胞系中保持为惰性单体。通过重新引入外源性HSF 3基因，使HSF 3缺失细胞恢复到接近正常的热休克反应状态。这些结果表明，HSF 3在热休克反应的调节中具有主导作用，并直接影响HSF 1的活性。
The vertebrate genome encodes a family of heat shock factors (HSFs 1–4) of which the DNA‐binding and transcriptional activities of HSF1 and HSF3 are activated upon heat shock. HSF1 has the properties of a classical HSF and exhibits rapid activation of DNA‐binding and transcriptional activity upon exposure to conditions of heat shock and other stresses, whereas HSF3 typically is activated at higher temperatures and with distinct delayed kinetics. To address the role of HSF3 in the heat shock response, null cells lacking the HSF3 gene were constructed by disruption of the resident gene by somatic recombination in an avian lymphoid cell line. Null cells lacking HSF3, yet expressing normal levels of HSF1, exhibited a severe reduction in the heat shock response, as measured by inducible expression of heat shock genes, and did not exhibit thermotolerance. At intermediate heat shock temperatures, where HSF1 oligomerizes to an active trimer in wild‐type cells, HSF1 remained as an inert monomer in the HSF3 null cell line. HSF3 null cells were restored to a nearly normal heat shock‐responsive state by reintroduction of an exogenous HSF3 gene. These results reveal that HSF3 has a dominant role in the regulation of the heat shock response and directly influences HSF1 activity.