哺乳动物SIRT1抑制了叉头转录因子
Maria Carla Motta1, Nullin Divecha, Madeleine Lemieux
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell
|February 26, 2004
概括
哺乳动物SIRT1 deacetylates像Foxo3a这样的头因子,抑制它们的活性并减少亡. 这与酵母和虫形成鲜明对比,这可能解释了卡路里限制如何促进长寿.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 衰老研究研究 衰老研究
背景情况:
- 依赖NAD的脱乙酶SIR2和分叉体转录因子调节模型生物的寿命.
- 在C. elegans中,SIR2和分叉蛋白与基因相互作用,影响寿命.
研究的目的:
- 为了研究哺乳动物SIR2基因组 (SIRT1) 和哺乳动物叉转录因子 (例如,Foxo3a) 之间的相互作用.
- 阐明SIRT1在调节叉活动中的作用及其对衰老和亡的影响.
主要方法:
- 生物化学试验以证明SIRT1.1对Foxo3a的脱乙化.
- 分析SIRT1对分叉因子的转录活性的影响.
- 哺乳动物发现与C. elegans遗传相互作用的比较.
主要成果:
- SIRT1去乙基化并抑制哺乳动物叉转录因子的活性,包括Foxo3a.
- 通过SIRT1介导的分叉蛋白的抑制减少了分叉依赖性亡.
- 此外,SIRT1还抑制瘤抑制剂p53,类似于它对叉因子的影响.
结论:
- 哺乳动物SIRT1负面调节叉头转录因子,反对在C. elegans中观察到的遗传相互作用.
- 通过SIRT1降低分叉蛋白和p53的调节可能会在像卡路里限制这样的条件下促进寿命延长.
相关概念视频
Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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...
Master Transcription Regulators
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...
Riboswitches
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
Transcriptional Regulation: Riboswitches
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...


