安诺基的调节:MEKK-1的激活需要通过caspases进行切割
M H Cardone1, G S Salvesen, C Widmann
1The Burnham Institute, La Jolla, California 92037, USA.
Cell
|July 25, 1997
概括
当细胞从细胞外基质中脱离时,细胞经历了亡,或anoikis. 这一过程涉及Jun N-终端酶 (JNK) 途径,需要酶活性,激活MEKK-1,创建一个促进细胞死亡的反循环.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 阿诺基斯是一种被编程的细胞死亡,由细胞对细胞外基质的粘附性丧失引发.
- Jun N-终端激酶 (JNK) 途径与阿诺基斯有关,但其上游调节者仍然不完全理解.
- 众所周知,卡斯巴酶活性在年夜期间对JNK通路激活至关重要.
研究的目的:
- 为了研究参与JNK通路激活的特定酶在 anoikis.
- 为了阐明MEKK-1裂变在年夜病中的作用.
- 为了描述 caspases 和 MEKK-1 之间的反循环在 anoikis.
主要方法:
- 在脱离的细胞中分析酶活性.
- 局部定向突变发生,以产生抗裂变的MEKK-1突变体.
- 野生类型和突变MEKK-1的过度表达研究.
- 对亡和caspase-7激活的评估.
主要成果:
- 一种特定于DEVD动机的酶在失去矩阵接触时切割MEKK-1,这对于MEKK-1激酶激活至关重要.
- 过度表达的MEKK-1裂变产物会诱导亡,而野生类型的MEKK-1会使细胞对anoikis敏感.
- 抗裂变或无激酶活性的MEKK-1突变分子部分保护细胞免受菌的侵袭,并抑制完全的caspase-7激活.
结论:
- 卡斯巴酶介导的MEKK-1裂变是激活JNK通路的关键步骤.
- 这种裂变事件启动了一个积极的反循环,激活的MEKK-1进一步促进了酶活性,放大了apoptotic信号.
- MEKK-1充当关键的调解者,将矩阵脱离与卡斯巴酶依赖的亡联系起来.
相关概念视频
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
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01:30Apoptosis
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01:24Caspases
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01:17The Extrinsic Apoptotic Pathway
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01:31The Intrinsic Apoptotic Pathway
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