プロゲステロン受容体の核局所化のメカニズム:モノマー間の相互作用の証拠

A Guiochon-Mantel¹, H Loosfelt, P Lescop

¹Hormones et Reproduction, INSERM U 135, Faculté de Médecine, Le Kremlin-Bicêtre, France.

Cell

|June 30, 1989

まとめ

ウサギのプロゲステロン受容体核の局所化は,構成信号配列とホルモン活性化DNA結合ドメイン相互作用の2つのメカニズムを含む. これらの経路は,細胞内の受容体輸送と機能を調節する.

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
エンドクリノロジーエンドクリノロジー

背景:

プロゲステロン受容体 (PR) は,プロゲステロンに対する反応として遺伝子発現を調節する重要な核受容体です.
PR核の局所化のメカニズムを理解することは,様々な生理学的および病理学的プロセスにおけるその役割を理解するために不可欠です.

研究の目的:

ウサギのプロゲステロン受容体の核輸入と局所化を制御する明確なメカニズムを解明する.
核へのPR転移に責任のある特定の領域と相互作用を特定する.

主な方法:

ウサギのプロゲステロン受容体の削除変異体の構築と分析.
モノクローナル抗体を使用して,細胞内の受容体の局所化を追跡します.
ホルモンのリガンドの存在と欠如における受容体の行動を調査する.

主要な成果:

アミノ酸638-642の間で構成的に活性な核の局所化信号が特定されました.
この信号配列の削除により,細胞プラズマの局所化が生じ,ホルモンが核の輸入を可能にしました.
ホルモン結合は,ステロイド結合ドメイン経由で,細胞質および核PRモノマーの両方の二重化および核転位を誘導した.

結論:

ウサギのプロゲステロン受容体は,核の局所化のために少なくとも2つの独立した経路を使用します.
信号配列は構成核インポートを媒介し,リガンド結合は受容体二分化と核移転を含むホルモン依存メカニズムを活性化させる.

さらに関連する動画

10:05

Visualization of Protein-protein Interaction in Nuclear and Cytoplasmic Fractions by Co-immunoprecipitation and In Situ Proximity Ligation Assay

Published on: January 16, 2017

09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

関連する概念動画

02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...

01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...

01:46

Nuclear Localization Signals and Import

Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...

01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...

01:42

Directionality of Nuclear Transport

01:45

Regulation of Nuclear Protein Sorting

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...

関連する実験動画