相关实验视频
Updated: Jul 22, 2026

13:21
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
通过适配蛋白Daxx激活亡信号调节激酶1 (ASK1) 的激活
H Y Chang1, H Nishitoh, X Yang
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02138, USA.
概括
Fas死亡受体通路通过Daxx蛋白激活Jun NH2-终端激酶 (JNK) 信号,该蛋白与ASK1激酶相互作用并激活,促进细胞亡.
科学领域:
- 细胞信号通道是细胞信号通道.
- 细胞亡和细胞死亡
- 分子生物学分子生物学
背景情况:
- 该Fas死亡受体启动细胞亡.
- 达克斯是一种与Fas受体相关的蛋白质.
- Jun NH2-终端激酶 (JNK) 路径的激活在亡中至关重要.
研究的目的:
- 阐明Daxx在Fas介导的JNK激活中的作用.
- 在Fas信号通路中识别Daxx和ASK1之间的相互作用.
- 要了解Daxx如何调节ASK1激酶活性.
主要方法:
- 野生类型和酶缺乏ASK1突变的过度表达.
- 分析Fas和Daxx诱导的亡.
- 对JNK激活的评估.
- 同免疫沉研究蛋白质相互作用.
主要成果:
- 达克斯激活了JNK激酶激酶ASK1.1.
- 酶缺乏ASK1突变的过度表达抑制了Fas和Daxx诱导的亡和JNK激活.
- 激活Fas促进了Daxx与ASK1.1的相互作用.
- 达克斯结合缓解ASK1的分子内抑制,激活其激酶活性.
结论:
- 达克斯-ASK1相互作用对于Fas诱导的JNK激活和亡至关重要.
- 这项研究定义了从Fas受体到JNK通路激活的信号级联.
- 这些发现揭示了通过受体相关蛋白调节ASK1激酶活性的机制.
相关概念视频
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 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...
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...
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...

