CtBP1的转录核心压缩活性是由ISG15修改调节的
Yun Hwan Lim1, Yoon Jin Park1, Jieun Lee1
1Department of Biological Sciences, Inha University, Incheon, Korea.
Animal cells and systems
|February 26, 2024
概括
干扰素α治疗将C端结合蛋白1 (CtBP1) 与ISG15结合在一起. 这种ISGylation增强了CtBP1的作用.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 后翻译修改 后翻译修改
背景情况:
- C端结合蛋白1 (CtBP1) 是一个关键的转录核心抑制剂,与癌症进展有关.
- CtBP1招募基因基因修饰酶来调节基因表达.
- 已知CtBP1的翻译后修改包括无处不在,酸化和SUMOylation.
研究的目的:
- 为了研究CtBP1通过干扰素刺激基因15 (ISG15) 的结合.
- 探索CtBP1ISGylation对其转录活性和蛋白质相互作用的功能后果.
主要方法:
- 用干扰素-α.治疗HeLa细胞.
- 对内源性CtBP1ISGylation的分析.
- 对CtBP1ISGylation进行调节酶 (USP18,EFP) 的鉴定.
- 评估CtBP1与相关蛋白质 (HDAC1,LSD1,HDAC4) 之间的结合亲和关系.
- 对CtBP1在EMT和亡相关基因上的转录抑制活动的评估.
主要成果:
- 内源性CtBP1在干扰素α治疗后经历ISGylation.
- ISGylation过程受USP18和EFP的监管.
- ISGylation 增强了 CtBP1 与 HDAC1 和 LSD1 的结合,但不是 HDAC4.
- ISG15修饰增强了CtBP1在EMT和亡基因上的转录抑制活性.
结论:
- ISG15结合改变了CtBP1的功能和活性.
- CtBP1 ISGylation为CtBP1介导的癌症提供了新的见解.
- 这一发现可能为癌症治疗中的治疗策略开辟新的途径.
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
Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
Inheritance 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
Prokaryotic Transcriptional Activators and Repressors
8.4K
8.4K
Eukaryotic Transcription Inhibitors
9.8K
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...
9.8K
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


