Ca2+誘発による転写因子MEF2の放出によって媒介されるT細胞のアポトーシス
1Center for Cancer Research, Department of Biology, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|October 26, 1999
まとめ
カルシウムシグナル伝達は,Cabin1とカルモジュリン経由でMEF2転写因子を活性化し,T細胞受容体の関与後にNur77発現とT細胞アポトシスを制御します.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 細胞シグナル伝達 細胞信号伝達
背景:
- T細胞受容体 (TCR) 信号伝達は,カルシウム依存遺伝子発現を含むチモサイトアポプトシスを誘発する.
- Nur77とNor1は,この過程における重要なステロイド受容体であり,Nur77の発現は,肌細胞増強因子2 (MEF2) によって調節される.
- カルシウムシグナル伝達とMEF2活性化を結びつける正確なメカニズムは不明のままである.
研究 の 目的:
- TCRの関与,カルシウム流入,およびNur77の発現につながるMEF2の活性化をつなぐシグナル伝達経路を解明する.
- T細胞アポトーシス中のMEF2活動の調節におけるCabin1とカルモジュリンの役割を調査する.
主な方法:
- TCR刺激に対する反応として,Cabin1,MEF2,およびカルモジュリンとの相互作用を調査した.
- 細胞内カルシウム濃度の変化と,タンパク質複合体の形成に及ぼす影響を分析した.
主要な成果:
- MEF2は,キャビン1によって不活性状態で隔離されます.
- TCRの関与は細胞内カルシウムを増加させ,カルモジュリンがCabin1.1に結合する.
- この競争的結合は,MEF2を解放し,その活性化と,その後のNur77プロモーターの活動を可能にします.
結論:
- Cabin1,MEF2,calmodulinを含む新しいシグナル伝達経路は,TCR誘発のNur77発現を媒介する.
- この経路は,T細胞アポトーシスの調節に不可欠です.
- この発見は,チモサイト選択の分子メカニズムに関する新しい洞察を提供します.
関連する概念動画
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
01:16Cell Motility through Blebbing
Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Blebbing Through the Matrix
In multicellular...
01:18Role of Myosin in Cell Migration
Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction. It is...
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction. It is...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.