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LRWD1 Regulates Microtubule Nucleation and Proper Cell Cycle Progression in the Human Testicular Embryonic Carcinoma Cells

机译:LRWD1调节人体睾丸胚胎癌细胞中的微管成核和适当的细胞周期进展

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摘要

ABSTRACT Leucine‐rich repeats and WD repeat domain containing protein 1 (LRWD1) is a testis‐specific protein that mainly expressed in the sperm neck where centrosome is located. By using microarray analysis, LRWD1 is identified as a putative gene that involved in spermatogenesis. However, its role in human male germ cell development has not been extensively studied. When checking in the semen of patients with asthenozoospermia, teratozoospermia, and asthenoteratozoospermia, the level of LRWD1 in the sperm neck was significantly reduced with a defective neck or tail. When checking the sub‐cellular localization of LRWD1 in the cells, we found that LRWD1 resided in the centrosome and its centrosomal residency was independent of microtubule transportation in NT2/D1, the human testicular embryonic carcinoma, cell line. Depletion of LRWD1 did not induce centrosome re‐duplication but inhibited microtubule nucleation. In addition, the G1 arrest were observed in LRWD1 deficient NT2/D1 cells. Upon LRWD1 depletion, the levels of cyclin E, A, and phosphorylated CDK2, were reduced. Overexpression of LRWD1 promoted cell proliferation in NT2/D1, HeLa, and 239T cell lines. In addition, we also observed that autophagy was activated in LRWD1 deficient cells and inhibition of autophagy by chloroquine or bafilomycin A1 promoted cell death when LRWD1 was depleted. Thus, we found a novel function of LRWD1 in controlling microtubule nucleation and cell cycle progression in the human testicular embryonic carcinoma cells. J. Cell. Biochem. 119: 314–326, 2018. ? 2017 Wiley Periodicals, Inc.
机译:富含含有蛋白质1(LRWD1)的富含亮氨酸的重复和WD重复域是睾丸特异性蛋白,其主要在离心体所在的精子颈部。通过使用微阵列分析,将LRWD1鉴定为参与精子发生的推定基因。然而,它在人类雄性细胞发育中的作用尚未得到广泛研究。在患有哮喘患者的患者的精液时,无颈部或尾部的精子颈部的LRWD1水平显着降低。当检查细胞中LRWD1的亚细胞定位时,发现LRWD1驻留在中心体和其中心居留力,与NT2 / D1,人睾丸胚胎癌,细胞系中的微管运输无关。 LRWD1的耗竭不会诱导Centroosome重复,但抑制微管成核。此外,在LRWD1不足的NT2 / D1细胞中观察到G1停滞。在LRWD1耗尽时,细胞周期蛋白E,A和磷酸化CDK2的水平降低。 LRWD1的过度表达LRWD1促进NT2 / D1,HELA和239T细胞系中细胞增殖。此外,我们还观察到,在LRWD1缺乏细胞中激活自噬,并在LRWD1耗尽时通过氯喹或BafiLomycin A1抑制自噬促进细胞死亡。因此,我们发现LRWD1的新功能在控制人睾丸胚胎癌细胞中的微管成核和细胞周期进展中。 J.Cell。生物学习。 119:314-326,2018 2017年Wiley期刊,Inc。

著录项

  • 来源
    《Journal of cellular biochemistry.》 |2018年第1期|共13页
  • 作者单位

    Department of Cell Biology and AnatomyNational Cheng Kung UniversityTainan 701 Taiwan;

    Department of Biological Sciences and TechnologyNational University of TainanTainan 700 Taiwan;

    Department of Cell Biology and AnatomyNational Cheng Kung UniversityTainan 701 Taiwan;

    Department of Obstetrics and GynecologyChi‐Mei Medical CenterTainan Taiwan;

    Department of Biological Sciences and TechnologyNational University of TainanTainan 700 Taiwan;

    Department of Cell Biology and AnatomyNational Cheng Kung UniversityTainan 701 Taiwan;

    Department of Biological Sciences and TechnologyNational University of TainanTainan 700 Taiwan;

    Department of Obstetrics and GynecologyNational Cheng Kung UniversityTainan 701 Taiwan;

    Department of UrologyNational Cheng Kung UniversityTainan 701 Taiwan;

    Department of Biological Sciences and TechnologyNational University of TainanTainan 700 Taiwan;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    LRWD1; CENTROSOME; CELL CYCLE; MICROTUBULE NUCLEATION; AUTOPHAGY;

    机译:lrwd1;centrosome;细胞周期;微管成核;自噬;

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