核受容体の冷却誘導性共同活性化剤で,適応性熱生成と関連しています
1Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell
|April 7, 1998
まとめ
研究者らは,身体の熱生成である適応性熱生成を活性化するタンパク質であるPGC-1を発見した. この発見は,エネルギーバランスを理解し,肥満に対する防御策を開発するために極めて重要です.
科学分野:
- メタボリック調節 メタボリック調節
- 分子生物学は分子生物学である.
- 肥満に関する研究.
背景:
- 適応性発熱は,エネルギーホメオスタシスと肥満の予防に不可欠です.
- 熱生成の分子メカニズムを理解することは,代謝疾患の研究の鍵です.
研究 の 目的:
- 適応性熱生成に関与する新しい転写協活性化物質を特定する.
- 発熱遺伝子の調節におけるPGC-1の役割を明らかにする.
主な方法:
- 茶色の脂肪組織のcDNAから,新しい転写共同活性化剤であるPGC-1のクローニング.
- マウスの寒さへの反応として,PGC-1 mRNA発現の分析.
- 解離タンパク質1 (UCP-1) プロモーター活性に対するPGC-1の影響を評価する.
- 白い脂肪細胞におけるPGC-1の遺伝子発現とミトコンドリア生体生成への影響を評価.
主要な成果:
- PGC-1 mRNAレベルは,寒さにさらされたときに茶色の脂肪と骨格筋で有意に増加します.
- PGC-1は,UCP-1プロモーターのPPARgammaと甲状腺ホルモン受容体の転写活動を強化する.
- 白いアディポサイトにおける子宮外PGC-1発現は,UCP-1とミトコンドリア呼吸連鎖酵素を誘導する.
- PGC-1はアディポサイト内のミトコンドリアDNA含有量を増加させます.
結論:
- PGC-1は,核受容体と適応性熱生成の転写制御を結びつけ,重要な共同活性化剤として作用する.
- この発見は,肥満と代謝機能障害に対する介入のための分子標的を提供します.
- PGC-1は,寒さへの被曝に対する代謝適応を媒介する重要な役割を果たします.
関連する概念動画
02:04Co-activators and Co-repressors
8.9K
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...
8.9K
02:04Co-activators and Co-repressors
3.2K
No description available
3.2K
01:31Transducer Mechanism: Nuclear Receptors
5.4K
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:
5.4K
01:26Thermoregulation
3.1K
The human body has a sophisticated thermoregulation system that employs negative feedback mechanisms to maintain an optimal core temperature. When the core temperature drops, peripheral and central thermoreceptors send signals to the hypothalamus, activating the heat-promoting center. This center triggers several responses aimed at increasing the core temperature. First, vasoconstriction reduces the flow of warm blood from internal organs to the skin so that the heat is not lost from the skin,...
3.1K
02:26NF-κB-dependent Signaling Pathway
10.3K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
10.3K
02:42Eukaryotic Transcription Activators
13.3K
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...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
13.3K