Myc 9aaTAD激活域与具有优越的高 afinity 的转录媒介结合
Andrea Knight1,2,3, Josef Houser4,5,6, Tomas Otasevic7
1School of Life Science, Faculty of Science and Engineering, Anglia Ruskin University, East Road, Cambridge, CB1 1PT, UK. andrea.knight@aru.ac.uk.
Molecular medicine (Cambridge, Mass.)
|November 13, 2024
概括
在癌症中准MYC基因是困难的. 研究人员在c-Myc中确定了两个关键域,乙-TAD和9aaTAD,它们一起工作以激活,提供了一个潜在的新治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- MYC基因过度表达在人类癌症中很常见,包括脑瘤.
- MYC蛋白质本质上是无序的,这使得它们很难被药物准.
- 九种氨基酸激活域 (9aaTAD) 是MYC蛋白中的一个关键功能区域.
研究的目的:
- 识别和描述c-Myc瘤基因中的功能域.
- 为了研究c-Myc域和协同激活剂之间的相互作用.
- 探索针对MYC驱动的癌症的新型治疗策略.
主要方法:
- 使用预测算法识别c-Myc.中的9aaTAD.
- 进行了交换活化试验,以测试短c-Myc的功能.
- 在一个单一混合试验中,生成并测试了带有和没有9aaTAD的c-Myc构造.
- 描述了乙-TAD域及其与9aaTAD的协作.
- 使用生物物理方法研究了Myc激活域和CBP联合激活器的KIX域之间的相互作用.
主要成果:
- 证实9aaTAD (区域100-108) 是c-Myc.中的一个关键激活域.
- 一个新的协作域,乙-TAD (区域69-103),被确定和描述.
- 9aaTAD的存在与转录激活有很强的相关性.
- 在Myc-9aaTAD和CBP KIX域之间观察到强大的纳米分子相互作用.
- 发现9aaTADs在MYC家族中得到保护.
结论:
- c-Myc瘤基因的激活功能由乙-TAD和9aaTAD域共同调解.
- c-Myc与CBP KIX域之间的相互作用为c-Myc驱动的瘤提供了可用药物的标.
- 了解这些领域为开发向癌症治疗提供了新的途径.
关键词:
9aaTADAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTAD 9aaTad 9aaTad 9aaTad 9aaTad 9aaTad 9aaTad 9aaTad 9aaTad 9aaTad 9aaaTad 9aaTad 9aaTad 9aaTad 9aaTad 9aaaTad 9aaTad 9aaTad 9aaTad 9aaTad 9aaTad 9aaTad 9aaTad 9美国中央银行 (CBP) 的CBP.这就是KIXIX.迈克·迈克是我的一个朋友.我的cNN 在线观看相关概念视频
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Eukaryotic Transcription Activators
10.9K
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
10.9K
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
RNA Polymerase II Accessory Proteins
9.1K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.1K
Cooperative Binding of Transcription Regulators
6.4K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.4K
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


