HEF1依赖的Aurora A激活诱导了初级膜的分解
Elena N Pugacheva1, Sandra A Jablonski, Tiffiney R Hartman
1Division of Basic Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Cell
|July 3, 2007
概括
哺乳动物的毛,关键的细胞传感器,通过涉及HEF1和Aurora A (AurA) 激酶的途径分解,激活HDAC6. 这一发现揭示了AurA的新作用,并建议治疗状腺相关疾病的治疗点.
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:
- 哺乳动物的毛是重要的细胞传感器,参与许多发育和病理过程.
- 纤毛相关信号通路的缺陷与各种疾病有关.
- 控制毛形成和拆卸的机制在很大程度上是未知的.
研究的目的:
- 为了阐明控制状细胞分解的细胞机制.
- 为了确定参与纤毛再吸收的关键蛋白质和途径.
- 探索潜在的治疗策略,以眼稳定为目标.
主要方法:
- 研究了的基底体中的蛋白质相互作用.
- 利用生物化学分析来评估蛋白质酸化和酶活性.
- 采用小分子抑制剂来调节路径活性.
- 在细胞模型中观察到对状细胞结构和稳定性的影响.
主要成果:
- 前列腺增生蛋白HEF1与毛体的基底体中的奥罗拉A (AurA) 激酶相互作用.
- 这种相互作用导致HDAC6的酸化和激活,HDAC6是一种氨酸脱乙酶.
- 激活HDAC6促进了状细胞的分解 (再吸收).
- 这一途径对于纤毛吸收是必要的,也是足够的,它代表了AurA的非性功能.
结论:
- 一个涉及HEF1,AurA和HDAC6的新途径调节了哺乳动物的状细胞分解.
- 紫外线A激酶在控制状细胞再吸收方面具有意想不到的非线性作用.
- 抑制AurA和HDAC6可以稳定乳毛,这表明潜在的临床应用在治疗与乳毛功能障碍相关的疾病.
相关概念视频
02:17Separation of Sister Chromatids
3.6K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.6K
01:22Microtubules in Signaling
1.5K
The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
1.5K
00:50Anaphase Promoting Complex
2.5K
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...
2.5K
01:39Mechanism of Filopodia Formation
2.5K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.5K
01:05Mechanism of Ciliary Motion
4.9K
The ciliary structures were first seen in 1647 by Antonie Leeuwenhoek while observing the protozoans. In lower organisms, these appendages are responsible for cell movement, while in higher organisms, these appendages help in the movement of the extracellular fluids within the body cavities.
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
4.9K
01:35Disassembly of Intermediate Filaments
2.0K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.0K