德罗斯菲拉IKK相关的激酶通过IAPs的降解来调节caspases的非apoptotic功能
Erina Kuranaga1, Hirotaka Kanuka, Ayako Tonoki
1Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Cell
|August 5, 2006
概括
德罗斯菲拉IKK相关酶 (DmIKKε) 通过促进DIAP1降解来调节非apoptotic酶活性. 这种激酶为酶功能建立了值,这对发育至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 发育生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 酶激活主要研究在亡中,但它们在非亡细胞功能中的作用不太清楚.
- 在细胞灭亡之外调节卡斯帕斯的机制在很大程度上是未知的.
- 草 IAP1 (DIAP1) 是一种关键的卡斯帕酶抑制剂,对发育细胞死亡调节至关重要.
研究的目的:
- 为了确定在非apoptotic背景下caspase激活的调节者.
- 阐明Drosophila IKK相关酶 (DmIKKε) 在控制酶活性中的作用.
- 了解DmIKKε如何影响DIAP1蛋白水平和非apoptotic caspase功能.
主要方法:
- 研究了DmIKKε在DIAP1.1上的酸化活性.
- 利用了DmIKKε在Drosophila翅膀形象性磁盘proneural集群中的淘汰实验.
- 评估DmIKKε操纵对DIAP1稳定性和感官器官前体 (SOP) 发育的影响.
主要成果:
- DmIKKε直接酸化并促进DIAP1.1的降解.
- 敲除DmIKKε导致DIAP1稳定在翼形象性磁盘前神经.
- 破坏DmIKKε会影响Drosophila SOP的发育,这表明它在非apoptotic caspase介导的过程中发挥了作用.
结论:
- DmIKKε是DIAP1蛋白水平的关键调节者.
- DmIKKε 确定了非apoptotic 细胞功能所需的 caspase 活动的值.
- 这项研究揭示了一种新的机制,该机制控制了非apoptotic发育过程中的caspase活性.
相关概念视频
Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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...
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...
Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...


