メニンはAP1の転写因子JunDと相互作用し,JunDが活性化する転写を抑制する
S K Agarwal1, S C Guru, C Heppner
1Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. sunitaa@amb.niddk.nih.gov
Cell
|February 16, 1999
まとめ
腫瘍抑制メニン (MEN1遺伝子から) は,直接転写因子JunDと結合する. この相互作用は,JunDを抑制する.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- がん研究 がん研究
背景:
- 腫瘍抑制遺伝子MEN1は,未定の機能を有する核タンパク質であるメニンをコードする.
- メニンの分子相互作用を理解することは,腫瘍抑制におけるメニンの役割を明らかにするために重要である.
研究 の 目的:
- メニンと相互作用するタンパク質を特定する.
- メニン-ジュンD相互作用の機能的影響を調査する.
主な方法:
- 酵母2ハイブリッドスクリーニングにより,相互作用するパートナーを特定します.
- タンパク質の相互作用を確認するためのインビトロおよびインビボアッセイ.
- 転写活性を評価するためのレポーター遺伝子アッセイ.
主要な成果:
- トランスクリプションファクターJunDを直接的なメンリン結合パートナーとして特定しました.
- 複数の実験的アプローチを用いて,meni-JunDの相互作用が確認されました.
- メニンはJunD媒介による転写活性化を抑制することが示された.
- MEN1変異が,JUNDとのメニンの相互作用を妨害することを示した.
結論:
- メニンの腫瘍抑制作用は,JunD.に直接結合することで媒介される.
- JunD活性化転写の阻害は,メニンの腫瘍抑制機能の重要なメカニズムです.
- メニン-ジュンDの相互作用は,腫瘍発達の予防におけるMEN1の役割にとって極めて重要です.
さらに関連する動画
関連する概念動画
Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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 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...
Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...


