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NCB：华人科学家解析GSK3促进肿瘤发生的重要机制

2016-08-17 佚名 生物谷

GSK3肿瘤
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来自美国MD安德森癌症中心的研究人员最近在国际学术期刊Nature Cell Biology上发表了一项最新研究进展，他们发现位于细胞核内的糖原合成酶激酶3beta（GSK3beta）通过调节组蛋白甲基化影响基因表达发挥癌基因作用促进肿瘤发生。该研究为癌症治疗提供了重要靶点。 越来越多的证据表明GSK3beta在多种肿瘤类型中发挥癌基因作用，但是其中的机制仍然没有被完全了解。而深入了解其中的


来自美国MD安德森癌症中心的研究人员最近在国际学术期刊Nature Cell Biology上发表了一项最新研究进展，他们发现位于细胞核内的糖原合成酶激酶3beta（GSK3beta）通过调节组蛋白甲基化影响基因表达发挥癌基因作用促进肿瘤发生。该研究为癌症治疗提供了重要靶点。

越来越多的证据表明GSK3beta在多种肿瘤类型中发挥癌基因作用，但是其中的机制仍然没有被完全了解。而深入了解其中的机制可以为开发癌症靶向药物找到新靶点。

在这项研究中，研究人员首先发现细胞核内的GSK3beta能够导致组蛋白去甲基化酶KDM1A在细胞核内稳定积累，对于肿瘤发生过程中组蛋白H3K4甲基化水平调节起关键作用。GSK3beta能够在CD1alpha对KDM1A的Ser687进行磷酸化之后再对KDM1A的Ser683进行磷酸化。

这样的磷酸化模式会诱导KDM1A与一种叫做USP22的去泛素化酶结合，随后被USP22去泛素化，导致KDM1A在细胞核内稳定存在。研究人员发现在肿瘤发生过程中组蛋白H3K4的去甲基化需要GSK3beta和USP22介导的KDM1A稳定，H3K4甲基化水平的变化又抑制了BMP2,CDKN1A以及GATA的转录，导致癌症干细胞的自我更新和胶质母细胞瘤的发生。

研究人员还在人类胶质母细胞瘤样本中对上述结果进行了求证，他们发现KDM1A的表达水平与细胞核内GSK3beta和USP22的表达水平存在相关性。随后他们又进一步使用了一种GSK3抑制剂，tideglusib，处理肿瘤异种移植小鼠模型，结果表明该药物能够促进肿瘤异种移植小鼠模型对化疗的敏感性，导致KDM1A的表达水平发生下调，促进小鼠存活。

这项研究深入揭示了GSK3beta促进肿瘤发生的重要机制，表明细胞核内GSK3beta和USP22介导的组蛋白去甲基化酶KDM1A的稳定对于胶质母细胞瘤的发生非常重要，为开发靶向治疗药物提供了新方向。

原始出处

Aidong Zhou, Kangyu Lin, Sicong Zhang, Yaohui Chen, Nu Zhang, Jianfei Xue, Zhongyong Wang, Kenneth D. Aldape, Keping Xie, James R. Woodgett & Suyun Huang.Nuclear GSK3β promotes tumorigenesis by phosphorylating KDM1A and inducing its deubiquitylation by USP22.NCB.2016

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    2017-04-13 anminleiryan

    #GSK3#

    0

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    2017-03-08 hongbochen

    #解析#

    0

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beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Aug 18 13:13:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100305, encodeId=5d5710030572, content=学习了，赞一个！, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Aug 18 13:13:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100307, encodeId=9d1b10030e36, content=学习了，赞一个！, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Aug 18 13:13:00 CST 2016, time=2016-08-18, status=1, ipAttribution=)]
    2016-08-20 136****0753赵

    值得学习

    0

  4. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100307, encodeId=9d1b10030e36, content=学习了，赞一个！, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Aug 18 13:13:00 CST 2016, time=2016-08-18, status=1, ipAttribution=)]
    2016-08-19 ms4468361851264128

    #华人#

    0

  5. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100307, encodeId=9d1b10030e36, content=学习了，赞一个！, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Aug 18 13:13:00 CST 2016, time=2016-08-18, status=1, ipAttribution=)]
    2016-08-18 1dd8a7c5m95(暂无匿称)

    学习了，赞一个！

    0

  6. 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beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Aug 18 13:13:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100305, encodeId=5d5710030572, content=学习了，赞一个！, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Aug 18 13:13:00 CST 2016, time=2016-08-18, status=1, 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    2016-08-18 1dd8a7c5m95(暂无匿称)

    学习了，赞一个！

    0

  7. 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    2016-08-18 1dd8a7c5m95(暂无匿称)

    学习了，赞一个！

    0

  8. 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    2016-08-18 1dd8a7c5m95(暂无匿称)

    学习了，赞一个！

    0

  9. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100307, encodeId=9d1b10030e36, content=学习了，赞一个！, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Aug 18 13:13:00 CST 2016, time=2016-08-18, status=1, ipAttribution=)]
    2016-08-18 1dd8a7c5m95(暂无匿称)

    学习了，赞一个！

    0

  10. 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createdName=hongbochen, createdTime=Wed Mar 08 09:48:00 CST 2017, time=2017-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101566, encodeId=363c101566d9, content=值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLMzGpMQ8w4I7FpiblCXNcmI6O7TDINutbaicEUpoYFR1rWqn3kTbulfMhT0iaPFurLz2ddEcWe3BiciaQ/0, createdBy=5f6e1724878, createdName=136****0753赵, createdTime=Sat Aug 20 15:27:00 CST 2016, time=2016-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581917, encodeId=ea1c158191ee3, content=<a href='/topic/show?id=830c35868ec' target=_blank style='color:#2F92EE;'>#华人#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35868, encryptionId=830c35868ec, topicName=华人)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3f7716881423, createdName=ms4468361851264128, createdTime=Fri Aug 19 05:48:00 CST 2016, time=2016-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100345, encodeId=c68410034535, content=学习了，赞一个！, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Aug 18 15:08:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100314, encodeId=0775100314f8, content=学习了，赞一个！, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, 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    2016-08-18 1dd8a7c5m95(暂无匿称)

    学习了，赞一个！

    0

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