スプライスされたX-ボックスの結合タンパク質1は,mTORの活性化によって適応的成長を刺激する
Xiaoding Wang1, Yingfeng Deng2, Guangyu Zhang1
1Division of Cardiology (X. Wang, G.Z., C.L., G.D., H.I.M., D.H.T., X.L., D.L.L., A.F., T.G.G., Z.V.W.), Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Circulation
|June 11, 2019
まとめ
XBP1sによって調節される展開されたタンパク質反応は,心筋細胞の成長に極めて重要です. この経路はFKBP11とmTORを含み,心不全の進行と心機能に影響を与えます.
科学分野:
- 心血管生物学
- 細胞 の ストレス 反応
- 分子心臓科
背景:
- 展開されたタンパク質反応 (UPR) は細胞生理学と疾患において不可欠であるが,心臓肌細胞の成長の調節におけるその役割は十分に理解されていない.
- 心臓の機能と機能不全を理解するには,UPRと心臓細胞の成長の関連を調査することが不可欠です.
研究 の 目的:
- UPR,特にXBP1s (spliced X-box binding protein 1) が心筋細胞の増殖を調節する役割を明らかにする.
- UPR信号と心臓細胞の成長を結びつける分子メカニズムを定義する.
主な方法:
- 心臓組織における機能増減方法を用いたXBP1sの遺伝子操作
- 主要な心筋細胞培養を用いて細胞自律成長効果を研究する.
- XBP1sとFKBP11 (FK506結合タンパク質11) の発現をヒトとネズミの心不全モデルで分析した.
主要な成果:
- XBP1sの発現はヒトとネズミの心不全で低下しています.
- XBP1sの欠乏は心不全を悪化させ,その心的過剰表現は機能障害を予防する.
- XBP1sは,FKBP11- mTORシグナル伝達軸を通して,適応性のある心臓の成長を促進する.
結論:
- XBP1s- FKBP11- mTOR経路は,UPRと心臓細胞の成長を結びつける重要なレギュラーである.
- この経路をターゲットにすることで 心不全の治療策を提案できます
- この研究は,UPRによる心臓適応の新たなメカニズムを特定した.
関連する概念動画
Alternative RNA Splicing
24.7K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
24.7K
RNA Splicing
60.4K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.4K
mTOR Signaling and Cancer Progression
4.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.7K
Factors Affecting Protein-Drug Binding: Protein-Related Factors
535
Drug binding to proteins is a key aspect of pharmacokinetics and can influence a drug's distribution, absorption, and elimination in the body. Several factors, including the drug's physiochemical properties, protein concentration, disease states, and the number of binding sites on the protein, influence this process.
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...
535
The Equilibrium Binding Constant and Binding Strength
14.9K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
14.9K
Ligand Binding and Linkage
5.5K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.5K


