狼敏感性等位基 PBX1D 的分子机制
Yuk Pheel Park1, Tracoyia Roach2, Sujung Soh3
1Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health, San Antonio, TX.
Journal of immunology (Baltimore, Md. : 1950)
|July 24, 2023
概括
在狼患者中发现的主导阴性PBX1D异型,会损害T细胞功能. 转录后的变化,包括蛋白质不稳定和局部变化,有助于PBX1D.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 预B细胞白血病Homeobox 1 (PBX1) 是一种调节基因表达和染色质可访问性的转录因子.
- 一种主导负拼接异型,PBX1D,缺乏DNA结合域,在狼患者和小鼠的CD4+T细胞中被上调.
- 在CD4+T细胞中PBX1D过度表达会破坏调节性T细胞平衡,并促进炎症性T细胞扩张.
研究的目的:
- 研究调节PBX1D功能的转录后机制及其在系统性红斑狼 (SLE) 中CD4+T细胞炎症中的作用.
主要方法:
- 在激活的CD4+T细胞和B细胞中分析PBX1表达.
- 评估PBX1D蛋白质的稳定性和降解途径 (ubiquitin-proteasome系统).
- 在PBX1B.中的假定泛素结合位点 (K292-293) 的位点定向突变发生.
- 评估PBX1B和PBX1D亚细胞局部化,有或没有MEIS/PREP1辅因子.
主要成果:
- 在CD4+ T细胞和B细胞中激活后,PBX1信息表达被下调.
- PBX1D 蛋白质本质上不如 PBX1B 稳定,并通过无素-蛋白酶体通路降解.
- 在PBX1B中K292-293的突变模仿了PBX1D的不稳定性,并取消了DNA结合.
- 与PBX1B不同,PBX1D表现出辅因子独立的细胞质保留,表明核转位发生了变化.
结论:
- 多种转录后机制,包括蛋白质稳定性变化和核进口受损,导致PBX1D功能丧失.
- 这些机制是 CD4 + T 细胞炎症表型的诱导的基础,这种表型在系统性红斑狼中观察到.
相关概念视频
Pleiotropy
40.6K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.6K
Epistasis
47.0K
In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
47.0K
Genetic Lingo
103.2K
Overview
103.2K
Lethal Alleles
15.6K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.6K
Exon Recombination
3.6K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.6K
Genome-wide Association Studies-GWAS
13.6K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
13.6K


