在基因表达中,激活剂周转的假定刺激作用
J Russell Lipford1, Geoffrey T Smith, Yong Chi
1Howard Hughes Medical Institute, Division of Biology, MC 156-29, California Institute of Technology, 1200 E. California Boulevard, Pasadena, California 91125, USA.
Nature
|November 4, 2005
概括
无素-蛋白酶体系统 (UPS) 降解转录激活剂,但这种蛋白质分解可以悖论地增强基因表达. 抑制蛋白酶体会损害主要酵母激活剂的功能,如Gcn4.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 无素-蛋白酶体系统 (UPS) 调节蛋白质水平,并影响细胞过程.
- 转录激活剂是基因表达的关键决定因素.
- 在转录调节中UPS的作用是复杂的,有证据表明非蛋白质溶解功能.
研究的目的:
- 调查UPS-依赖蛋白解在刺激可诱导的转录激活剂的功能中的作用.
- 为了确定特定激活剂的蛋白质分解是否增强了它们的转录活性.
主要方法:
- 利用酵母模型研究转录激活剂Gcn4,Gal4和Ino2/4.4的功能.
- 采用蛋白酶体抑制和在无素连接酶 (SCF ((Cdc4)) 和无素中的特定突变.
- 评估了对目标基因转录和RNA聚合酶II协会的影响.
主要成果:
- 蛋白质酶抑制减少了对Gcn4,Gal4和Ino2/4.4的标的转录.
- 影响Gcn4无化和降解的突变损害了基因转录.
- 尽管Gcn4丰富度增加,但发生了转录缺陷,RNA聚合酶II关联减少.
结论:
- 通过UPS对某些转录激活剂的蛋白质分解可以刺激它们的功能.
- 在酵母中,UPS依赖的降解对诱导性转录激活剂的适当活性至关重要.
- 针对性的降解,而不是单纯的丰富性,对于激活器功能至关重要.
相关概念视频
RNA Polymerase II Accessory Proteins
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...
Co-activators and Co-repressors
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...
Eukaryotic Transcription Activators
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 domains are...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
Co-activators and Co-repressors
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...
Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...


