在HSF1中,压抑基因是由酸化调节的
Stefan Gabriel1, Thomas Czerny1, Elisabeth Riegel1
1Department of Applied Life Sciences, University of Applied Sciences, FH Campus Wien, Favoritenstraße 222, A-1100 Vienna, Austria.
Cellular signalling
|July 19, 2023
概括
热冲击因子1 (HSF1) 的激活通过酸化来调节. 这项研究确定了HSF1上抑制其转录活动的特定酸化部位 (S303),揭示了一种新的抑制机制.
科学领域:
- 分子生物学分子生物学
- 细胞应激反应的应激反应
背景情况:
- 热冲击因子1 (HSF1) 是一个关键的转录因子,调节细胞对蛋白质毒性压力的热冲击反应 (HSR).
- 虽然HSF1激活对细胞存活至关重要,但其精确的调节机制,特别是酸化的作用,仍然不完全理解.
研究的目的:
- 调查HSF1酸化在调节其转录活性中的作用.
- 为了确定负责HSF1激活或抑制的特定酸化部位和动机.
主要方法:
- 在已知的酸化位点上发生HSF1的突变,以产生模仿 (11 M(+)) 和减少 (11 M(-)) 的变种.
- 在各种压力条件下使用HSR记者等离子体测定交换活化潜力.
- 分析单个氨基酸替代的效果,特别是在S303/307图案上.
主要成果:
- 用热激活HSF1独立于酸化.
- 不同的细胞应力不同地影响HSF1变体的激活潜力.
- 酸化在血清303 (S303) 已被确定为唯一负责抑制HSF1活动.
- 发现一个独立于HSF1背景的小压制性动机降低了促进体转录的调节.
结论:
- HSF1酸化,特别是在S303,在调节其转录输出方面发挥着至关重要的作用.
- 一种新的HSF1抑制机制涉及一个小的动机,直接影响促进体活动,超出了以前已知的途径.
相关概念视频
Co-activators and Co-repressors
7.4K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.4K
Histone Modification
13.4K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.4K
Eukaryotic Transcription Inhibitors
9.9K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.9K
Covalently Linked Protein Regulators
6.9K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.9K
Phosphorylation
50.5K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.5K
The JAK-STAT Signaling Pathway
9.0K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.0K


