Caenorhabditis elegans HSF-1 is an essential nuclear protein that forms stress granule-like structures following heat shock.
Caenorhabditis elegans HSF-1 is an essential nuclear protein that forms stress granule-like structures following heat shock.
复制标题
DOI：
10.1111/acel.12024
复制
发表时间：
2013-02
期刊：
影响因子：
7.8
通讯作者：
Lamitina T
中科院分区：
文献类型：
--
作者：
Morton EA;Lamitina T
热休克转录因子（HSF）是热休克诱导基因表达的保守调控因子。通过对秀丽隐杆线虫HSF同源物HSF -1的研究，已经确定了HSF在发育、衰老和免疫等生理过程中的机体作用。然而，hsf-1在秀丽隐杆线虫中的分子和细胞生物学特性尚不完全清楚。我们制造了表达生理水平HSF-1::GFP融合蛋白的动物，并检测了其功能、定位和体内调控。通过挽救与两个HSF-1突变等位基因相关的表型的能力，GFP是功能性的。在dna结合缺陷突变体中，hsf-1胁迫、衰老和发育表型的恢复被取消，这表明即使在没有胁迫的情况下，hsf-1的转录靶点对其功能也至关重要。在非应激条件下，HSF-1::GFP主要存在于细胞核中。热休克后，HSF-1::GFP迅速可逆地重新分布到动态的亚核结构中，这些结构与人类核应激颗粒具有许多特性，包括与活性转录标记物共定位。HSF-1胁迫颗粒的快速形成需要HSF-1 DNA结合活性，而胁迫颗粒形成的阈值受生长温度的影响。HSF-1应激颗粒的形成不是由抑制IGF信号引起的，而IGF信号通路先前被认为在HSF-1的上游起作用。我们的研究结果表明，发育、应激和衰老途径可能以不同的方式调节HSF-1的功能，并且HSF-1核应激颗粒的形成是体内HSF-1调节的一个进化保守方面。
The heat shock transcription factor (HSF) is a conserved regulator of heat shock-inducible gene expression. Organismal roles for HSF in physiological processes such as development, aging, and immunity have been defined largely through studies of the single C. elegans HSF homolog, hsf-1. However, the molecular and cell biological properties of hsf-1 in C. elegans are incompletely understood. We generated animals expressing physiological levels of an HSF-1::GFP fusion protein and examined its function, localization, and regulation in vivo. HSF-1::GFP was functional as measured by its ability to rescue phenotypes associated with two hsf-1 mutant alleles. Rescue of hsf-1 stress, aging, and development phenotypes was abolished in a DNA-binding-deficient mutant, demonstrating that the transcriptional targets of hsf-1 are critical to its function even in the absence of stress. Under non-stress conditions, HSF-1::GFP was found primarily in the nucleus. Following heat shock, HSF-1::GFP rapidly and reversibly redistributed into dynamic, sub-nuclear structures that share many properties with human nuclear stress granules, including colocalization with markers of active transcription. Rapid formation of HSF-1 stress granules required HSF-1 DNA binding activity and the threshold for stress granule formation was altered by growth temperature. HSF-1 stress granule formation was not induced by inhibition of IGF signaling, a pathway previously suggested to function upstream of hsf-1. Our findings suggest that development, stress, and aging pathways may regulate HSF-1 function in distinct ways, and that HSF-1 nuclear stress granule formation is an evolutionarily conserved aspect of HSF-1 regulation in vivo.
登录
查看更多内容
影响因子：
64.5
作者：
Dai, Chengkai;Whitesell, Luke;Lindquist, Susan
通讯作者：
Lindquist, Susan
影响因子：
5.3
作者：
BALER, R;DAHL, G;VOELLMY, R
通讯作者：
VOELLMY, R
DOI：
10.1083/jcb.200109018
发表时间：
2002-03-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jolly C;Konecny L;Grady DL;Kutskova YA;Cotto JJ;Morimoto RI;Vourc'h C
通讯作者：
Vourc'h C
影响因子：
5.3
作者：
Inouye, S;Katsuki, K;Nakai, A
通讯作者：
Nakai, A
影响因子：
11.4
作者：
Jedlicka, P;Mortin, MA;Wu, C
通讯作者：
Wu, C