明らかにNF-kappa B転写因子の細胞質前駆体におけるDNA結合活性の活性化
1Whitehead Institute for Biomedical Research Cambridge, Massachusetts 02142.
Cell
|April 22, 1988
まとめ
カッパ増強剤結合タンパク質であるNF-カッパBは,刺激されていない細胞の細胞質に存在しますが,不活性です. フォルボールのエステルはNF-カッパB結合を活性化し,その核転位を引き起こします.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 免疫学 免疫学とは
背景:
- 核因子カッパB (NF-カッパB) は,免疫反応と細胞信号伝達に関与する重要な転写因子です.
- NF-kappa Bは,通常,刺激されていない細胞の無活性な細胞質の形態で発見されます.
- カッパ増強剤は,免疫グロブリンカッパのライトチェーン遺伝子発現に不可欠です.
研究 の 目的:
- カッパ免疫グロブリンライトチェーン発現が欠けている細胞におけるNF-カッパBの細胞の局所化と活性化状態を調査する.
- プレ-B細胞でNF-カッパBが調節されるメカニズムを決定する.
- NF-kappa B活性化と核転位におけるホルボエステルの役割を理解する.
主な方法:
- 70Z/3 プレ-B 細胞やHeLa 細胞などの細胞系を利用しています.
- タンパク質の活性性を評価するために,デナチュレーション,サイズ分化,再ナチュレーションを含む生化学的技術を使用します.
- デオキシコラートナトリウム,ホルマミドなどの解離剤を用いて,細胞分からNF-カッパBを抽出し,分析する.
- 非刺激細胞とホルボールエステル刺激細胞の両方の細胞溶液と核分子のNF-カッパBレベルを比較する.
主要な成果:
- NF-カッパBは,刺激されていない70Z/3細胞の細胞分泌部分で検出され,その存在が示され,DNA結合活動がないことが示されました.
- 刺激されていない70Z/3細胞では,活性化されていない細胞内NF-kappa Bの有意な量が見つかり,刺激された細胞の活性化された核NF-kappa Bと比較できます.
- Phorbolエステル治療は,NF-カッパB結合阻害の放出につながり,その転位を核に誘導しました.
- 70Z/3細胞とHeLa細胞の両方には,DNAに積極的に結合しないNF-kappa Bの細胞性形態が含まれています.
結論:
- 細胞性NF-カッパBは,70Z/3細胞とHeLa細胞の両方で抑制状態で存在します.
- フォルボールのエステルは,NF-カッパBの調節において,結合抑制を解放し,核転位を促すという二重の役割を果たします.
- これらの発見は,免疫細胞の発達と機能に関連するNF-kappa B活性化の重要な規制メカニズムを明らかにしています.
さらに関連する動画
関連する概念動画
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...
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...
Eukaryotic Transcription Inhibitors
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 DNA...
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
NF-κB-dependent Signaling Pathway
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 heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...


