Growth-arrest-specific protein 2 inhibits cell division in Xenopus embryos.
Growth-arrest-specific protein 2 inhibits cell division in Xenopus embryos.
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DOI：
10.1371/journal.pone.0024698
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Mandato CA
中科院分区：
文献类型：
--
作者：
Zhang T;Dayanandan B;Rouiller I;Lawrence EJ;Mandato CA
生长停滞特异性2基因最初在生长停滞条件下的鼠成纤维细胞中鉴定。此外，静止的、非分裂的细胞的血清刺激导致gas2的下调并导致重新进入细胞周期。细胞骨架重排对于细胞周期进程和细胞分裂是至关重要的，并且Gas2蛋白已被证明与肌动蛋白和微管在间期哺乳动物细胞中共定位。尽管有这些发现，支持Gas2在细胞分裂机制中的作用的直接证据尚未报道。为了确定Gas2蛋白是否在细胞分裂中起作用，我们在非洲爪蟾胚胎中过表达全长Gas2蛋白和含有肌动蛋白结合CH结构域或微管蛋白结合Gas2结构域的Gas2截短体。我们发现，全长Gas2蛋白和Gas2结构域，但不是CH结构域，抑制细胞分裂，导致多核细胞。Gas 2结构域单独可以阻止细胞分裂的观察表明Gas 2的功能是由微管结合介导的。Gas2共定位与微管在细胞皮质的Gas2注射非洲爪蟾胚胎使用冷冻共聚焦显微镜和共沉淀与微管在细胞骨架共沉淀试验。为了研究Gas2诱导的细胞分裂停滞的机制，我们使用创伤诱导的收缩阵列分析表明，Gas2稳定微管。最后，电子显微镜研究表明，Gas2将微管捆绑成更高阶的结构。我们的实验表明，Gas2抑制非洲爪蟾胚胎的细胞分裂。我们建议，Gas2功能介导的结合和捆绑微管，导致细胞分裂停滞。
Growth-arrest-specific 2 gene was originally identified in murine fibroblasts under growth arrest conditions. Furthermore, serum stimulation of quiescent, non-dividing cells leads to the down-regulation of gas2 and results in re-entry into the cell cycle. Cytoskeleton rearrangements are critical for cell cycle progression and cell division and the Gas2 protein has been shown to co-localize with actin and microtubules in interphase mammalian cells. Despite these findings, direct evidence supporting a role for Gas2 in the mechanism of cell division has not been reported. To determine whether the Gas2 protein plays a role in cell division, we over-expressed the full-length Gas2 protein and Gas2 truncations containing either the actin-binding CH domain or the tubulin-binding Gas2 domain in Xenopus laevis embryos. We found that both the full-length Gas2 protein and the Gas2 domain, but not the CH domain, inhibited cell division and resulted in multinucleated cells. The observation that Gas2 domain alone can arrest cell division suggests that Gas2 function is mediated by microtubule binding. Gas2 co-localized with microtubules at the cell cortex of Gas2-injected Xenopus embryos using cryo-confocal microscopy and co-sedimented with microtubules in cytoskeleton co-sedimentation assays. To investigate the mechanism of Gas2-induced cell division arrest, we showed, using a wound-induced contractile array assay, that Gas2 stabilized microtubules. Finally, electron microscopy studies demonstrated that Gas2 bundled microtubules into higher-order structures. Our experiments show that Gas2 inhibits cell division in Xenopus embryos. We propose that Gas2 function is mediated by binding and bundling microtubules, leading to cell division arrest.
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GAS2是一种生长逮捕特异性蛋白，是微丝网络系统的组成部分。
影响因子：
7.8
作者：
Brancolini, C;Bottega, S;Schneider, C
通讯作者：
Schneider, C
DOI：
10.1074/jbc.m111.242263
发表时间：
2011-07-15
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Stroud MJ;Kammerer RA;Ballestrem C
通讯作者：
Ballestrem C
DOI：
10.1083/jcb.200103105
发表时间：
2001-08-20
期刊：
The Journal of cell biology
影响因子：
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作者：
Mandato CA;Bement WM
通讯作者：
Bement WM
影响因子：
50.3
作者：
Petroulakis, Emmanuel;Parsyan, Armen;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum
影响因子：
9.2
作者：
Röper, K;Brown, NH
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