核受容体のような経路で,真菌の多剤耐性を調節する
Jitendra K Thakur1, Haribabu Arthanari, Fajun Yang
1Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA.
Nature
|April 4, 2008
まとめ
研究者らは,真菌の転写因子が多剤耐性 (MDR) をどのように調節するかを明らかにした. この研究は,真菌と脊椎動物の薬剤耐性に対する保存されたメカニズムを明らかにし,治療が難しい真菌感染症の新たな治療標的を提供している.
科学分野:
- 医学菌学 医学菌学について
- 分子生物学は分子生物学である.
- ドラッグ・ディスカバリー・ドリッグ・ディスカバリー・ドリッグ・ディスカバリー・ドリッグ・ディスカバリー
背景:
- 多剤耐性 (MDR) は,免疫力が低下した患者の好機的真菌感染症の治療を複雑にする.
- 菌類の亜鉛-クラスター転写因子による薬物の流出ポンプの増幅は,MDRの重要なメカニズムですが,十分に理解されていません.
研究 の 目的:
- 病原菌におけるMDRの基礎となる分子メカニズムを解明する.
- 薬剤耐性の真菌感染症と闘うための新しい治療標的を特定する.
主な方法:
- Saccharomyces cerevisiaeとCandida glabrataで研究されたPdr1pファミリーのメンバー.
- メディエーター共同活性化剤のGal11p/MED15サブユニットとそのKIXドメインの役割を分析した.
主要な成果:
- Pdr1pファミリーのメンバーは直接薬物に結合し,エフフルスポンプ発現とMDRを誘発する.
- 菌類の調節体と脊椎動物のPXR核受容体との間の機能的な類似性が発見されました.
- Gal11p/MED15サブユニットとそのKIXドメインは,MDR.を調節する上で重要な役割を果たします.
結論:
- 菌類の核受容体のような遺伝子調節経路の詳細な機構的理解.
- 多剤耐性キノコ感染症の治療のための新しい治療標的を特定しました.
関連する概念動画
01:28Yeast Signaling
15.7K
Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
15.7K
01:45Regulation of Nuclear Protein Sorting
2.5K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.5K
01:19Interactions Between Signaling Pathways
4.7K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
4.7K
01:26Signal Transduction: Overview
8.6K
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
8.6K
01:31Transducer Mechanism: Nuclear Receptors
6.6K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
6.6K
01:15Antifungal Agents
119
Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to...
119