Nuclear phosphatase PPM1G in cellular survival and neural development.

Nuclear phosphatase PPM1G in cellular survival and neural development.
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DOI:
10.1002/dvdy.23990
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发表时间:
2013-09
影响因子:
2.5
通讯作者:
Wang, Yibin
Wang, Yibin
中科院分区:
生物学3区
文献类型:
--
作者:
Foster, William H.;Langenbacher, Adam;Gao, Chen;Chen, Jaunian;Wang, Yibin

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PPM1G是一种核定位丝氨酸/苏氨酸磷酸酶,参与染色质重塑、mRNA剪接和DNA损伤的调节。然而,其在体内的功能尚不清楚。在小鼠和斑马鱼的发育过程中,ppm1g的表达在中枢神经系统中高度富集。在E12.5后,ppm1g−/−小鼠是胚胎致死的,具有不完全外显率。在ppm1g−/−胚胎中观察到吻侧缺陷,包括神经管和颅面缺陷,这与神经上皮细胞死亡增加有关。在斑马鱼中,ppm1g的缺失也会导致神经缺陷和异常的神经标记基因表达。来自ppm1g−/−胚胎的原代成纤维细胞在没有永生化的情况下不能生长,而永生化的ppm1g−/−成纤维细胞在氧化和基因毒性应激下的细胞死亡比野生型成纤维细胞增加。我们的体内和体外研究揭示了PPM1G在正常发育和细胞存活中的关键作用。
PPM1G is a nuclear localized serine/threonine phosphatase implicated to be a regulator of chromatin remodeling, mRNA splicing and DNA damage. However, its in vivo function is unknown. Here we show that ppm1g expression is highly enriched in the central nervous system during mouse and zebrafish development. ppm1g−/− mice were embryonic lethal with incomplete penetrance after E12.5. Rostral defects, including neural tube and craniofacial defects were observed in ppm1g−/− embryos associated with increased cell death in the neural epithelium. In zebrafish, loss of ppm1g also led to neural defects with aberrant neural marker gene expression. Primary fibroblasts from ppm1g−/− embryos failed to grow without immortalization while immortalized ppm1g−/− fibroblasts had increased cell death upon oxidative and genotoxic stress when compared to wild type fibroblasts. Our in vivo and in vitro studies revealed a critical role for PPM1G in normal development and cell survival.
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PPM1G/PP2Cgamma 对存活运动神经元 (SMN) 的去磷酸化控制着 SMN 复合体的卡哈尔体定位和稳定性。
DOI: 10.1083/jcb.200704163
发表时间: 2007-11-05
期刊: The Journal of cell biology
影响因子: --
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