在RD細胞中，prohibition - 2定位于核仁，調節核糖體RNA轉錄，促進細胞增殖

2018年1月，東北師范大學可用藥基因與蛋白篩選國家工程實驗室；東北師范大學遺傳與細胞學研究所；吉林大學**醫院腫瘤中心；齊齊哈爾醫科大學醫學與藥學研究所(National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China；Institute of Genetics and Cytology, Northeast Normal University, Changchun, 130024, China；Oncology Center, First Hospital, Jilin University, Changchun, 130021, China；Present address: Research Institute of Medical Science and Pharmacy, Qiqihar Medical University,Qiqihar, 161006, China) Luguo Sun老師研究團隊在《Scientific Reports》上發表論文：

“Prohibitin 2 localizes in nucleolus to regulate ribosomal RNA transcription and facilitate cell proliferation in RD cells”

“在RD細胞中，prohibition - 2定位于核仁，調節核糖體RNA轉錄，促進細胞增殖”

Abstract：

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.

摘要：

抑制素2 (Prohibitin 2, PHB2)是一種保守的多功能蛋白，傳統上定位于線粒體內膜，對維持線粒體功能至關重要。在這里，我們研究了PHB2在人橫紋肌肉瘤(RMS) RD細胞中的作用，發現PHB2在核仁中有大量的定位。我們證明了PHB2敲低通過誘導細胞周期阻滯和抑制DNA合成來抑制RD細胞增殖。同時，下調PHB2還可誘導部分RD細胞凋亡并促進分化。此外，通過透射電鏡觀察，PHB2沉默導致核仁形態改變，核仁功能受損，45S和18S核糖體RNA合成下調。一致地，PHB2敲除后，c-Myc在核糖體DNA (rDNA)啟動子上的占用被減弱，而更多的成肌細胞決定蛋白1 (MyoD)分子結合到rDNA啟動子上。綜上所述，我們的研究結果表明，核仁PHB2通過調節多種轉錄因子參與維持RD細胞核仁形態和功能，這可能是PHB2促進腫瘤增殖和抑制分化的潛在機制之一。我們的研究為RMS的發病機制和高度保守的PHB2蛋白的新特征提供了新的見解。

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