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当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

YY1 OPB肽抗癌活性的表征

卷 19, 期 6, 2019

页: [504 - 511] 页: 8

弟呕挨: 10.2174/1568009618666181031153151

价格: $65

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摘要

背景:阴阳1(YY1)的癌蛋白结合(OPB)结构域由G201和S226之间的26个氨基酸组成,参与YY1与多种癌基因产物的相互作用,包括MDM2,AKT,EZH2和E1A。通过OPB结构域,YY1促进癌细胞中这些癌蛋白的致癌或增殖调节。我们以前证明具有OPB序列的肽阻断YY1-AKT相互作用并抑制乳腺癌细胞增殖。 目的:在目前的研究中,我们对OPB结构域进行了表征,并确定了肽设计的最小区域以抑制癌细胞。 方法:使用丙氨酸扫描方法,我们发现OPB C-末端的氨基酸是YY1与AKT结合所必需的。进一步的研究表明,OPB中的丝氨酸和苏氨酸残基而非赖氨酸在YY1-AKT相互作用中起关键作用。我们生成GFP融合表达载体以表达具有连续缺失的N末端的OPB肽,并发现OPB1(即G201-S226)是细胞质的,但OPB2(即E206-S226),OPB3(即E206-S226)和对照肽都是核和细胞质。 结果:OPB1和2均抑制乳腺癌细胞增殖和迁移,但OPB3表现出与对照相似的作用。 OPB1和2导致细胞周期停滞在G1期,增加p53和p21表达,并且降低MCF-7细胞中的AKT(S473)磷酸化,但在MDA-MB-231细胞中没有。 结论:总体而言,OPB的丝氨酸和苏氨酸对于YY1与癌蛋白的结合是必需的,并且OPB肽可以最小化为E206-S226,其维持对YY1促进的细胞增殖的抑制活性。

关键词: YY1,OPB肽,蛋白质相互作用,抑制活性,抗癌活性,癌蛋白。

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图形摘要

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