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関連する概念動画

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

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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...
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Co-activators and Co-repressors02:04

Co-activators and Co-repressors

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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...
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RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

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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...
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Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

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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...
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Master Transcription Regulators02:23

Master Transcription Regulators

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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...
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Cell Specific Gene Expression01:58

Cell Specific Gene Expression

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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Updated: Nov 12, 2025

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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選択的CRAF阻害はトランザクションを誘発する

Charles W Morgan1, Ian L Dale2, Andrew P Thomas3

  • 1Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.

Journal of the American Chemical Society
|March 22, 2021
PubMed
まとめ

CRAF (RAFキナーゼ) を選択的に標的にすると,パラドックス的にRAFシグナリングが活性化され,仮説に反する. この研究では,CRAF抑制を調査するために,バイオオートホーガンリガンドテザリング (BOLT) を使用し,がん薬の発見への影響を明らかにしました.

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In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

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関連する実験動画

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科学分野:

  • 腫瘍学
  • 分子生物学
  • 薬理学について

背景:

  • アイソフォーム特有の薬の発見は困難であり,アイソフォームの規制の結果は不明である.
  • RAFキナーゼ (BRAF,CRAF) はMAPキナーゼシグナル伝達において重要な役割を果たし,がんではしばしば変異を起こします.
  • 現在のRAF阻害剤は,CRAF経由でパラドックスな活性化を引き起こし,耐性を引き起こします.

研究 の 目的:

  • 選択的CRAF抑制の効果を調査する.
  • CRAF選択的阻害がパラドックスの活性化を回避するかどうかを調べる.
  • 標的の検証のためのバイオ・オートゴーナル・リガンド・テザリング (BOLT) の有用性を実証する.

主な方法:

  • 選択的にCRAFへの阻害剤を標的とするバイオオートホーガンリガンドテザリング (BOLT) を利用した.
  • 選択的なCRAF阻害による下流信号の影響を調査した.

主要な成果:

  • 選択的CRAF阻害はRAF信号のパラドックスな活性化を促すことが判明しました.
  • この発見は,CRAF選択的抑制がパラドックスの活性化を回避するという仮説に異議を唱える.
  • 薬剤発見の初期段階の標的分類の方法として BOLT を実証した.

結論:

  • 選択的CRAF阻害は,より広範なRAF阻害に類似したパラドックスの活性化につながる可能性があります.
  • BOLTは薬の開発初期に 特定のタンパク質同型を標的とした結果の評価に 役立つツールです
  • CRAFの役割を理解することは 効果的ながん治療法と薬剤耐性の克服に不可欠です