大墙酶的基质Arpp19通过抑制蛋白酸酶2A来控制线粒分裂
Aicha Gharbi-Ayachi1, Jean-Claude Labbé, Andrew Burgess
1Universités Montpellier 2 et 1, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, IFR 122, 1919 Route de Mende, 34293 Montpellier cedex 5, France.
概括
大墙激酶 (Gwl) 激活通过酸化Arpp19和α-Endosulfine来抑制蛋白酸酶2A (PP2A). 这种酸化促进了线粒体的进入,Arpp19是Xenopus蛋提取物中的关键.
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:
- 分解调节涉及环林B-Cdc2激活和蛋白酸酶2A (PP2A) 抑制.
- 蛋白质激酶Greatwall (Gwl) 通过抑制PP2A,对维持线粒分裂至关重要.
研究的目的:
- 阐明Gwl激活导致PP2A抑制的机制.
- 为了识别和表征Gwl的基质参与PP2A调节在线粒分裂过程中.
主要方法:
- 使用Xenopus蛋提取物研究了Gwl基质.
- 分析了Arpp19和α-Endosulfine的酸化状态.
- 评估了化基质与PP2A的相关性.
- 评估了Gwl活性对PP2A抑制和线粒体进入的影响.
主要成果:
- 确定了循环腺单调节蛋白19 (Arpp19) 和α-Endosulfine作为Gwl基质.
- 由Gwl对Arpp19和α-Endosulfine的酸化导致它们与PP2A的关联和抑制.
- 在没有Gwl活性的情况下,这些基质的脱化会降低它们的PP2A抑制能力.
- 内源的Arpp19,而不是α-Endosulfine,主要负责Xenopus蛋提取物中线性进入时的PP2A抑制.
结论:
- 通过Gwl介导的Arpp19和α-Endosulfine的酸化是抑制PP2A在线粒分裂过程中的关键机制.
- Arpp19在调节PP2A活动和促进Xenopus蛋提取物中线粒体进入方面发挥着关键作用.
相关概念视频
Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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...
Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...


