直接的リピートは,甲状腺ホルモン,レチノ酸,ビタミンD3受容体に対する選択的反応要素として直接的に繰り返されます
K Umesono1, K K Murakami, C C Thompson
1Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, San Diego, California 92186-5800.
Cell
|June 28, 1991
まとめ
直接的な重複型甲状腺ホルモン反応要素 (TREs) は,パリンドローム型TREsと異なる. ハーフサイト間隔は,選択的なホルモン反応を決定的に決定し,甲状腺ホルモン,レチノ酸,ビタミンD3の信号伝達に影響を与えます.
科学分野:
- 分子生物学は分子生物学である.
- エンドクリノロジー エンドクリノロジー
- 遺伝学 遺伝学とは
背景:
- 甲状腺ホルモン反応要素 (TRE) は,遺伝子発現を調節する.
- TREsの構造,特に半サイト配置は,受容体結合と下流シグナル伝達に影響します.
- TRE構造のニュアンスを理解することは,ホルモン調節の解読に不可欠です.
研究 の 目的:
- 直接繰り返しの半サイトアレンジメントを持つ新しいTREsを特定し,特徴づけること.
- TRE機能と選択性に対する半サイト間隔の影響を調査する.
- 微分ホルモン受容体結合におけるDNA配列と間隔の役割を明らかにする.
主な方法:
- 直接繰り返されるTREの識別.
- 甲状腺ホルモン (T3),レチノ酸,ビタミンDに対する反応を評価するための機能検査3.
- 観察されたホルモン反応とDNA結合の相関関係.
主要な成果:
- 直接的な繰り返しTREを特定し,特徴づけました.
- パリンドローム型TREとは異なり,直接繰り返されたTREはレチノ酸反応をもたらさなかった.
- シングルヌクレオチドによる半サイト間隔の変更により,TREsはレチノ酸またはビタミンD3応答要素に変換され,T3応答は失われます.
- 結果は,それぞれのホルモン受容体のDNA結合親和性に相関する.
結論:
- タンデムリピートホルモンの反応要素は,一般的に生物学的調節において重要である.
- TREsの半部位置間隔は,選択的ホルモン反応を達成するための重要なコードとして機能します.
- この発見は,内分泌のシグナル伝達経路を理解し,標的療法を開発するための意味を持つ.
関連する概念動画
01:08Intracellular Hormone Receptors
Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
01:26Receptor Tyrosine Kinases
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
01:31Transducer Mechanism: Nuclear Receptors
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:
01:20Synthesis and Regulation of Thyroid Hormones
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
01:18Functions of Thyroid Hormones
The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...