Blood:为什么感染埃博拉病毒会增加患淋巴瘤的风险?

2017-10-30 qinqiyun MedSci原创

埃博拉病毒(EBV)在大部分人类宿主的B淋巴细胞中持续存在,与多种B细胞淋巴瘤相关。潜伏感染期,EBV翻译合成隐匿膜蛋白2A(LMP2A)来模拟宿主B细胞受体(BCR)的信号通路,以此维持B细胞存活。在活体内研究LMP2A在淋巴瘤发生过程的作用,研究人员发现在转基因小鼠模型中,LMP2A通过使B细胞逃逸p53信号通路介导的MYC-诱导的细胞凋亡,从而使MYC所驱动的淋巴瘤快速发生。

关键点:

LMP2A可增强MYC的表达,然后通过Cks1快速降解p27kip1肿瘤抑制因子。

Cks1失活,可恢复肿瘤抑制因子p27kip1的表达水平,并延缓LMP2A介导的淋巴瘤发生。

摘要:

埃博拉病毒(EBV)在大部分人类宿主的B淋巴细胞中持续存在,与多种B细胞淋巴瘤相关。潜伏感染期,EBV翻译合成隐匿膜蛋白2A(LMP2A)来模拟宿主B细胞受体(BCR)的信号通路,以此维持B细胞存活。

在活体内研究LMP2A在淋巴瘤发生过程的作用,研究人员发现在转基因小鼠模型中,LMP2A通过使B细胞逃逸p53信号通路介导的MYC-诱导的细胞凋亡,从而使MYC所驱动的淋巴瘤快速发生。

然而,LMP2A促进转录的机制尚不明确,Kamonwan Fish等人近期研究发现LMP2A可通过增强MYC的表达和肿瘤抑制因子p27kip1 MYC依赖性的降解来促进B细胞增生。

衔接蛋白(Cks1,SCFSkp2泛素化连接酶复合物的辅因子、MYC的下游靶点)失活,可增加恶性肿瘤前期p27kip1的表达。

在表达LMP2A的小鼠中,Cks1缺陷可减轻脾脏重量、修复B细胞滤泡形成、抑制前肿瘤B细胞的细胞周期进展,从而延长MYC驱动的肿瘤发生。

Kamonwan Fish等人的研究表明,LMP2A利用MYC在细胞周期中的作用,特别是在p27kip1降解过程中,来加速活体内淋巴瘤的生成。研究结果揭示了EBV影响MYC在恶性转化中的作用的新的机制,为靶向EBV在细胞周期中的作用提供理论。

原始出处:

Kamonwan Fish,et al.EBV latent membrane protein 2A orchestrates p27kip1 degradation via Cks1 to accelerate MYC-driven lymphoma in mice.Blood  2017  :blood-2017-07-796821;  doi: https://doi.org/10.1182/blood-2017-07-796821

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createdBy=12f71314239, createdName=ann y, createdTime=Mon Oct 30 23:02:18 CST 2017, time=2017-10-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=257314, encodeId=2c2425e3141b, content=不错的文章值得一读, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Mon Oct 30 22:01:23 CST 2017, time=2017-10-30, status=1, ipAttribution=)]
    2017-10-31 cqykthl

    不是很明白

    0

  4. 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    2017-10-31 周周人

    学习.

    0

  5. 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    2017-10-30 ann y

    为什么感染埃博拉病毒会增加患淋巴瘤的风险?

    0

  6. 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createdBy=12f71314239, createdName=ann y, createdTime=Mon Oct 30 23:02:18 CST 2017, time=2017-10-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=257314, encodeId=2c2425e3141b, content=不错的文章值得一读, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Mon Oct 30 22:01:23 CST 2017, time=2017-10-30, status=1, ipAttribution=)]
    2017-10-30 ann y

    为什么感染埃博拉病毒会增加患淋巴瘤的风险?

    0

  7. 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createdBy=12f71314239, createdName=ann y, createdTime=Mon Oct 30 23:02:18 CST 2017, time=2017-10-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=257314, encodeId=2c2425e3141b, content=不错的文章值得一读, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Mon Oct 30 22:01:23 CST 2017, time=2017-10-30, status=1, ipAttribution=)]
    2017-10-30 ann y

    为什么感染埃博拉病毒会增加患淋巴瘤的风险?

    0

  8. 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createdBy=12f71314239, createdName=ann y, createdTime=Mon Oct 30 23:02:18 CST 2017, time=2017-10-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=257314, encodeId=2c2425e3141b, content=不错的文章值得一读, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Mon Oct 30 22:01:23 CST 2017, time=2017-10-30, status=1, ipAttribution=)]
    2017-10-30 ann y

    为什么感染埃博拉病毒会增加患淋巴瘤的风险?

    0

  9. 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    2017-10-30 ann y

    为什么感染埃博拉病毒会增加患淋巴瘤的风险?

    0

  10. 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    2017-10-30 1e1b8538m79(暂无匿称)

    不错的文章值得一读

    0

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