Identification of nucleolus-localized PTEN and its function in regulating ribosome biogenesis
Identification of nucleolus-localized PTEN and its function in regulating ribosome biogenesis
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DOI：
10.1007/s11033-014-3518-6
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发表时间：
2014-10-01
影响因子：
2.8
通讯作者：
Fang, Jugao
中科院分区：
文献类型：
--
作者：
Li, Pingdong;Wang, Danni;Fang, Jugao
肿瘤抑制基因PTEN是一种脂质磷酸酶，在不同类型的人类癌症中发现突变。PTEN通过抑制细胞膜上的PI3K-Akt信号通路抑制细胞增殖。然而，PTEN也被证明定位在细胞核中，在那里它通过一种不同的、未知的机制显示出肿瘤抑制活性。在本研究中，我们报道了PTEN也定位于核仁，并且核仁PTEN在调节核仁稳态和维持核仁形态方面起着重要作用。在PTEN缺失细胞中过表达核PTEN可抑制Akt的磷酸化并缩小细胞大小。PTEN阳性细胞中PTEN基因被敲除后，核仁形态发生改变，核仁较多的细胞比例增加。此外，PTEN阳性细胞中PTEN基因的敲除增加了核糖体的生物合成。这些发现扩大了目前对核定位PTEN功能和相关性的理解，并为开发针对PTEN的新疗法提供了基础。
The tumor suppressor PTEN is a lipid phosphatase that is found mutated in different types of human cancers. PTEN suppresses cell proliferation by inhibiting the PI3K-Akt signaling pathway at the cell membrane. However, PTEN is also demonstrated to localize in the cell nucleus where it exhibits tumor suppressive activity via a different, unknown mechanism. In this study we report that PTEN also localizes to the nucleolus and that nucleolar PTEN plays an important role in regulating nucleolar homeostasis and maintaining nucleolar morphology. Overexpression of nuclear PTEN in PTEN null cells inhibits Akt phosphorylation and reduces cell size. Knockdown of PTEN in PTEN positive cells leads to nucleolar morphologic changes and an increase in the proportion of cells with a greater number of nucleoli. In addition, knockdown of PTEN in PTEN positive cells increased ribosome biogenesis. These findings expand current understanding of function and relevance of nuclear localized PTEN and provide a foundation for the development of novel therapies targeting PTEN.