Prohibitin 2 localizes in nucleolus to regulate ribosomal RNA transcription and facilitate cell proliferation in RD cells.
Prohibitin 2 localizes in nucleolus to regulate ribosomal RNA transcription and facilitate cell proliferation in RD cells.
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禁止素2位于核仁中，以调节核糖体RNA转录并促进RD细胞中的细胞增殖。
DOI：
10.1038/s41598-018-19917-7
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发表时间：
2018-01-24
影响因子：
4.6
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Zhou Z;Ai H;Li K;Yao X;Zhu W;Liu L;Yu C;Song Z;Bao Y;Huang Y;Wu Y;Zheng L;Sun Y;Wang G;Ma K;Sun L;Li Y
Prohibitin 2(PHB2)是一种保守的多功能蛋白，传统上定位于线粒体内膜，是维持线粒体功能所必需的。在这里，我们研究了PHB2在人类横纹肌肉瘤(RMS)RD细胞中的作用，发现PHB2在核仁中有大量的定位。我们证明PHB2基因敲除通过诱导细胞周期停滞和抑制DNA合成来抑制RD细胞的增殖。同时，下调PHB2还可诱导部分RD细胞发生凋亡并促进其分化。此外，在透射电子显微镜下观察到，PHB2沉默导致核仁形态改变，并损害核仁功能，其证据是45S和18S核糖体RNA合成下调。一致地，当PHB2被敲除后，c-Myc在核糖体DNA(RDNA)启动子上的占位减少，而更多的成肌细胞决定蛋白1(MyoD)分子结合到rDNA启动子上。总之，我们的研究结果表明，核仁PHB2通过调节多种转录因子参与维持RD细胞的核仁形态和功能，这可能是PHB2促进肿瘤增殖和抑制分化的潜在机制之一。我们的研究为RMS的发病机制提供了新的见解，并为高度保守的PHB2蛋白提供了新的特征。
Prohibitin 2 (PHB2), as a conserved multifunctional protein, is traditionally localized in the mitochondrial inner membrane and essential for maintenance of mitochondrial function. Here, we investigated the role of PHB2 in human rhabdomyosarcoma (RMS) RD cells and found substantial localization of PHB2 in the nucleolus. We demonstrated that PHB2 knockdown inhibited RD cell proliferation through inducing cell cycle arrest and suppressing DNA synthesis. Meanwhile, down-regulation of PHB2 also induced apoptosis and promoted differentiation in fractions of RD cells. In addition, PHB2 silencing led to altered nucleolar morphology, as observed by transmission electron microscopy, and impaired nucleolar function, as evidenced by down-regulation of 45S and 18S ribosomal RNA synthesis. Consistently, upon PHB2 knockdown, occupancy of c-Myc at the ribosomal DNA (rDNA) promoter was attenuated, while more myoblast determination protein 1 (MyoD) molecules bound to the rDNA promoter. In conclusion, our findings suggest that nucleolar PHB2 is involved in maintaining nucleolar morphology and function in RD cells by regulating a variety of transcription factors, which is likely to be one of the underlying mechanisms by which PHB2 promotes tumor proliferation and represses differentiation. Our study provides new insight into the pathogenesis of RMS and novel characterizations of the highly conserved PHB2 protein.
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DOI：
10.2147/ahmt.s44582
发表时间：
2014
期刊：
Adolescent health, medicine and therapeutics
影响因子：
--
作者：
Egas-Bejar D;Huh WW
通讯作者：
Huh WW
影响因子：
4.8
作者：
Kasashima, Katsumi;Ohta, Eriko;Endo, Hitoshi
通讯作者：
Endo, Hitoshi
DOI：
10.1073/pnas.0800970105
发表时间：
2008-05-06
影响因子：
11.1
作者：
Ali, Syed A.;Zaidi, Sayyed K.;Stein, Janet L.
通讯作者：
Stein, Janet L.
影响因子：
1.7
作者：
Equilibrina, I.;Matsunaga, S.;Fukui, K.
通讯作者：
Fukui, K.
DOI：
10.1038/nrc3961
发表时间：
2015-07
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Kashi VP;Hatley ME;Galindo RL
通讯作者：
Galindo RL