抑癌基因Pdcd4的表达调控及产物泛素化研究进展
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Proceedings on The Expression of Tumor Suppressor Gene Pdcd4 and Ubiquitin Pathway of Pdcd4 Protein
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    摘要:

    程序性细胞死亡因子4 (programmed cell death 4,Pdcd4) 基因是近年新发现的一种抑癌基因,它的表达产物通过抑制相关基因的转录和翻译抑制肿瘤生成.Pdcd4在多种人肿瘤组织细胞中表达缺失或低表达.有研究发现,5’CpG岛的甲基化可能是脑胶质瘤中Pdcd4基因沉默的主要原因之一.另外,在多种肿瘤细胞中发现microRNA-21的表达水平与Pdcd4蛋白的表达呈负相关性,microRNA-21在转录后水平调控Pdcd4,其作用位点位于Pdcd4 mRNA的3′-UTR区.肿瘤细胞中Pdcd4的表达水平与细胞对抗肿瘤药物的敏感性有关,上调Pdcd4表达会增加细胞对某些抗肿瘤药物的敏感性,反之,下调Pdcd4表达则会引起某些药物细胞毒活性的减弱.有些药物本身也可以影响细胞中Pdcd4的表达水平.Pdcd4可以抑制p53的乙酰基化.Pdcd4蛋白能被蛋白激酶Akt/PKB磷酸化,引起Pdcd4的核易位,并减弱Pdcd4对转录激活因子AP-1的抑制作用.Pdcd4可以被蛋白激酶S6K1磷酸化并在泛素连接酶SCFβTRCP介导下经泛素化途径降解.

    Abstract:

    Programed cell death 4 (Pdcd4) is a newly discovered tumor suppressor gene,which was found to inhibit oncogenesis by suppressing transcription and translation related genes. Expression of Pdcd4 has been found loss or low in several types of human tumors. It is reported that 5’CpG island methylation is the predominant cause of Pdcd4 mRNA silencing in gliomas. MicroRNA-21 regulates Pdcd4 in post-transcription by binding Pdcd4, and the target site is at the Pdcd4 mRNA 3’-UTR region. The mean Pdcd4 protein levels in cells is correlated with the antitumor activity of some drugs, upregulation of Pdcd4 expression may increase cytotoxicity of certain antitumor drugs and downregulation of Pdcd4 expression may reduce cytotoxicity of certain antitumor drugs. Some antitumor drug may affect the expression of Pdcd4. Pdcd4 interferes with the acetylation of p53. Phosphorylation of Pdcd4 by Akt/PKB (protein kinase B) causes nuclear translocation of Pdcd4 and a decreased ability to function as an inhibitor of AP-1( activator protein-1)-mediated transcription. Phosphorylated Pdcd4 by protein kinase S6K1 can be degraded via the ubiquitin pathway by SCFβTRCP ligase.

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曹春明,孙震晓.抑癌基因Pdcd4的表达调控及产物泛素化研究进展[J].生物化学与生物物理进展,2010,37(4):353-357

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历史
  • 收稿日期:2009-10-13
  • 最后修改日期:2009-12-17
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  • 在线发布日期: 2009-12-22
  • 出版日期: 2010-04-20