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関連する概念動画

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

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 heterodimer of NF-κB...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

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 heterodimer of NF-κB...

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関連する実験動画

Updated: Jul 5, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

TNF-αは,2つの異なるカスパース-8活性化経路を誘導する.

Lai Wang1, Fenghe Du, Xiaodong Wang

  • 1Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

Cell
|May 20, 2008
PubMed
まとめ

腫瘍死滅因子アルファ (TNF-alpha) は,2つの異なる経路を通じてアポトーシスを引き起こす. これらの経路は,サイクロヘキシミドまたはSmacミメティックを含み,cIAP1/2およびc-FLIP経由でカスパース-8の活性化を差異的に調節します.

科学分野:

  • 細胞生物学 細胞生物学
  • 細胞死亡の分子メカニズム
  • 免疫学 免疫学とは

背景:

  • 腫瘍死滅因子アルファ (TNF-alpha) は,炎症反応における重要なサイトカインです.
  • 炎症からアポトーシスへの切り替えは,重要な細胞プロセスです.
  • カスパース-8は,TNF-α誘発アポトーシスの中心的なメディエーターです.

研究 の 目的:

  • TNF-αがアポトーシスを誘発する明確な分子機構を解明する.
  • カスパース-8活性化の調節におけるサイクロヘキシミドとSmacミメチックの役割を調査する.
  • TNF-αシグナル伝達におけるc-FLIPとcIAP1/2の調節機能を区別する.

主な方法:

  • タンパク質合成阻害剤であるサイクロヘキシミドを使用した.
  • スマック・ミメティック (Smac mimetic) を採用し,スマック/ディアブロ (Smac/Diablo) の小さな分子を真似した.
  • カスパース-8,c-FLIP,cIAP1/2,RIPK1,CYLDの関与を調査した.

主要な成果:

  • サイクロヘキシミドは,c-FLIPを分解することによって,カスパース-8の活性化を促進する.
  • Smac mimeticは,cIAP1/2を分解してアポトーシスを誘発し,RIPK1を放出し,カスパース-8活性化複合体を形成します.

さらに関連する動画

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

関連する実験動画

Last Updated: Jul 5, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

  • RIPK1は,Smacミメティック誘発によるが,サイクロヘキシミド誘発のカスパース-8活性化には不可欠である.
  • Smacミメティック誘発のカスパース-8活性化は,内生的なc-FLIPとは独立しています.
  • 結論:

    • TNF-αは,少なくとも2つの異なるカスパース-8活性化経路を通じてアポトシスを誘発する.
    • これらの経路は,細胞阻害剤 cIAP1/2 と c-FLIP によって差異的に調節されます.
    • これらの経路を理解することは,TNF-αシグナル伝達を含む疾患の標的治療戦略の洞察を提供します.