一个保存的prolyl-4-hydroxylases家族,可以修改HIF
1Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard L3.124, Dallas, TX 75390-9152, USA.
概括
高酸酶 (HPH) 酶对于检测细胞中的氧气水平至关重要. 这些酶向低氧诱导因子 (HIF) 进行降解,防止其在正常氧气条件下积累.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 哺乳动物细胞利用由低氧诱导因子 (HIF) 调节的保存途径来响应氧气变化.
- 在normoxia下,HIFα子单元通过一种ubiquitin-ligase复合体被降解,该复合体识别了基化林残留物.
研究的目的:
- 为了确定负责氧化HIF的酶.
- 研究这些酶在氧气感应中的作用.
主要方法:
- 一个保存的HIF prolyl hydroxylase (HPH) 酶家族的识别.
- 在哺乳动物细胞中同时表达HPH,观察对HIF积累的影响.
- 在Drosophila melanogaster细胞中的RNA干扰以抑制HPH和评估基因表达.
主要成果:
- 鉴定出HPH酶是负责HIF林氧化过程的.
- 在哺乳动物细胞中Normoxia下的HPH减弱HIF-1alpha积累的同时表达.
- 在Drosophila细胞中抑制HPH导致在normoxia下增加乳酸脱酶 (LDH) 基因表达.
结论:
- HPH酶是细胞氧气传感途径的重要组成部分.
- 在对氧水平的反应中,HPH在调节HIF稳定性和下游基因表达方面发挥着关键作用.
相关概念视频
Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Covalently Linked Protein Regulators
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.
Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Covalently Linked Protein Regulators
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.
Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...


