通过CDK9依赖的LSD1稳定,RNF20有助于表观遗传免疫抑制
Bo Dong1,2, Xinzhao Wang1,2,3, Xiang Song1,2,3,4
1Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508.
概括
循环素依赖性激酶9 (CDK9) 调节了基因沉默和免疫抑制. 它与RNF20的相互作用稳定了LSD1,影响了癌症免疫治疗的敏感性.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
- 免疫学 免疫学 免疫学
背景情况:
- 循环素依赖性激酶9 (CDK9) 对于转录和基因沉默至关重要.
- 抑制CDK9可增强免疫治疗的敏感性,但机制尚不清楚.
- 表观遗传调节会影响癌症中的免疫反应.
研究的目的:
- 阐明CDK9抑制影响癌症免疫疗法的机制.
- 研究RNF20和LSD1在CDK9-介导免疫抑制中的作用.
- 探索针对CDK9-RNF20-LSD1轴的治疗潜力.
主要方法:
- 通过ubiquitination和酸化试验研究了CDK9-RNF20-LSD1相互作用.
- 评估了RNF20和LSD1对基因素H3K4脱甲基和逆转录病毒抑制的影响.
- 在体内评估了RNF20损失对抗PD-1免疫疗法反应的影响.
- 在人类乳腺癌样本中的相关RNF20和LSD1水平.
主要成果:
- RNF20通过CDK9-依赖酸化和无处不在化稳定LSD1.
- 这种稳定对于组织素H3K4脱甲基化,逆转录病毒抑制和表观遗传免疫抑制至关重要.
- 丢失RNF20使癌细胞对抗PD-1疗法的敏感,这种效应可以通过LSD1.1.恢复.
- 在人类乳腺癌中,RNF20和LSD1的水平具有正相关性.
结论:
- RNF20在CDK9依赖的LSD1稳定中发挥着关键作用,调解表观遗传沉默和免疫抑制.
- 针对CDK9-RNF20-LSD1通路提供了增强癌症免疫治疗的潜在策略.
更多相关视频
10:44In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
Published on: May 5, 2023
1.4K
13:47Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models
Published on: March 29, 2019
9.6K
相关概念视频
01:37Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
02:26NF-κB-dependent Signaling Pathway
7.4K
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...
7.4K
03:17Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K
02:39lncRNA - Long Non-coding RNAs
8.6K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K
02:34Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
01:24Methods of Nuclear Reprogramming
1.8K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.8K