在CSFV感染期间,海斯H2B氨酸乳化调节NF-κB通过KPNA2响应
Wenhui Zhu1, Sen Zeng1, Shuaiqi Zhu1
1College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
International journal of biological macromolecules
|January 18, 2025
概括
基斯乳化,特别是在K16的H2B上,对于对病毒的天生的免疫力至关重要. 这种修改激活了NF-κB通路,促进了干扰素的产生,并抑制了病毒的复制.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
背景情况:
- 基因组 lysine 乳糖化 (Kla) 调节转录,炎症和免疫疾病.
- 基因素Kla在天生的免疫力和病毒感染中的作用基本上是未知的.
研究的目的:
- 在病毒感染期间研究基因素Kla在天生的免疫力中的机制.
- 为了确定特定的组织素乳化部位及其在古典猪瘟病毒 (CSFV) 感染中的作用.
主要方法:
- 在PK-15细胞中观察到光Kla信号在组织蛋白 (H2A,H2B,H3,H4) 中.
- 使用免疫沉来识别丰富的基因素Kla蛋白质,专注于H2B.
- 生成H2B K16R突变等离子体,以识别K16作为乳化部位.
- 使用Kla激动剂 (L-乳酸盐),抑制剂 (氧酸盐) 和siLDHA来研究LDHA-乳酸盐轴.
- 分析了H2B和CSFV NS4A蛋白之间的相互作用.
- 研究了H2B Kla对CSFV扩散的影响.
- 研究了NF-κB通路的激活,通过KPNA2进行p65核转位,以及III型干扰素 (IFN-λ) 表达.
主要成果:
- H2B是最丰富的乳酸化组合素.
- 鉴定出K16是H2B (H2BK16la) 上的一个乳化部位.
- 脊髓灰质炎病毒感染增加了全球H2B Kla和H2BK16la水平.
- 在全球和CSFV感染时,LDHA-乳酸盐轴对H2BK16la和泛Kla水平至关重要.
- H2B与CSFV NS4A蛋白进行相互作用.
- H2B Kla可以调节CSFV的扩散.
- H2BK16la和pan Kla通过KPNA2.2促进p65核转移来激活NF-κB通路.
- 这种激活导致III型干扰素 (IFN-λ) 表达的增加,抑制CSFV复制.
结论:
- H2B乳化对抗病毒感染的天生的免疫力起着重要作用.
- 该研究揭示了一种涉及H2B Kla,LDHA-乳酸盐轴,NF-κB通路激活和IFN-λ诱导在CSFV感染期间的新机制.
- 这些发现为病毒病原和病毒性疾病的潜在治疗策略提供了洞察力.
相关概念视频
NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
Co-activators and Co-repressors
7.3K
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...
7.3K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Histone Modification
13.0K
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...
13.0K
The Nucleosome Core Particle
853
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
853
Covalently Linked Protein Regulators
6.8K
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....
6.8K


