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Sci Adv：通过shRNA文库鉴定XBP1-u是MDM2/p53轴的新型调节剂

2017-11-02 MedSci MedSci原创

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活细胞中细胞周期进程是严格控制的基本过程，任何缺陷与各种异常紧密相关。肿瘤抑制因子p53/p21轴是控制细胞周期进程的核心通路，然而，其监管机制尚未得到充分阐述。为了阐明这个关键网络，研究人员筛选了一个短的发夹RNA表达载体文库，并将未剪切的X盒结合蛋白1（XBP1-u）确定为p53/p21轴的新型和关键调节因子。具体来说，XBP1-u通过增强p53泛素化来负调节p53/p21轴，这反过来可下调p

活细胞中细胞周期进程是严格控制的基本过程，任何缺陷与各种异常紧密相关。肿瘤抑制因子p53/p21轴是控制细胞周期进程的核心通路，然而，其监管机制尚未得到充分阐述。

为了阐明这个关键网络，研究人员筛选了一个短的发夹RNA表达载体文库，并将未剪切的X盒结合蛋白1（XBP1-u）确定为p53/p21轴的新型和关键调节因子。具体来说，XBP1-u通过增强p53泛素化来负调节p53/p21轴，这反过来可下调p21的表达。

该研究结果显示，XBP1-u抑制诱导G0-G1细胞周期停滞并抑制细胞增殖。进一步研究发现，由于密码子转移，XBP1-u的羧基末端与其剪接形式（XBP1-s）的羧基末端不同，通过抑制其自身泛素化与小鼠双分子同系物2（MDM2）蛋白结合并保持稳定。同时通过正调节MDM2，XBP-u过表达增强肿瘤发生。

总之，该研究结果表明，XBP1-u的功能远远不仅仅是作为XBP1的前体，而是参与基本的生物过程。此外，本研究提供了关于MDM2/p53/p21轴的调节的新见解。

原始出处：

Can Huang, Shourong Wu, et al., Identification of XBP1-u as a novel regulator of the MDM2/p53 axis using an shRNA library. Sci Adv. 2017 Oct; 3(10): e1701383. Published online 2017 Oct 18. doi: 10.1126/sciadv.1701383

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评论区 (3)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1746665, encodeId=2a0d1e466655a, content=<a href='/topic/show?id=8564114128c' target=_blank style='color:#2F92EE;'>#MDM2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11412, encryptionId=8564114128c, topicName=MDM2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fba635824905, createdName=wangyang7970, createdTime=Fri May 11 15:21:00 CST 2018, time=2018-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007696, encodeId=1c4e200e69635, content=<a href='/topic/show?id=f5cd188033b' target=_blank style='color:#2F92EE;'>#XBP1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18803, encryptionId=f5cd188033b, topicName=XBP1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=yeye5224612, createdTime=Wed Jul 25 05:21:00 CST 2018, time=2018-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372385, encodeId=d7c613e23851d, content=<a href='/topic/show?id=9d861362e53' target=_blank style='color:#2F92EE;'>#p53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13627, encryptionId=9d861362e53, topicName=p53)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Sat Nov 04 07:21:00 CST 2017, time=2017-11-04, status=1, ipAttribution=)]
    2018-05-11 wangyang7970

    #MDM2#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1746665, encodeId=2a0d1e466655a, content=<a href='/topic/show?id=8564114128c' target=_blank style='color:#2F92EE;'>#MDM2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11412, encryptionId=8564114128c, topicName=MDM2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fba635824905, createdName=wangyang7970, createdTime=Fri May 11 15:21:00 CST 2018, time=2018-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007696, encodeId=1c4e200e69635, content=<a href='/topic/show?id=f5cd188033b' target=_blank style='color:#2F92EE;'>#XBP1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18803, encryptionId=f5cd188033b, topicName=XBP1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=yeye5224612, createdTime=Wed Jul 25 05:21:00 CST 2018, time=2018-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372385, encodeId=d7c613e23851d, content=<a href='/topic/show?id=9d861362e53' target=_blank style='color:#2F92EE;'>#p53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13627, encryptionId=9d861362e53, topicName=p53)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Sat Nov 04 07:21:00 CST 2017, time=2017-11-04, status=1, ipAttribution=)]
    2018-07-25 yeye5224612

    #XBP1#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1746665, encodeId=2a0d1e466655a, content=<a href='/topic/show?id=8564114128c' target=_blank style='color:#2F92EE;'>#MDM2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11412, encryptionId=8564114128c, topicName=MDM2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fba635824905, createdName=wangyang7970, createdTime=Fri May 11 15:21:00 CST 2018, time=2018-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007696, encodeId=1c4e200e69635, content=<a href='/topic/show?id=f5cd188033b' target=_blank style='color:#2F92EE;'>#XBP1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18803, encryptionId=f5cd188033b, topicName=XBP1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=yeye5224612, createdTime=Wed Jul 25 05:21:00 CST 2018, time=2018-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372385, encodeId=d7c613e23851d, content=<a href='/topic/show?id=9d861362e53' target=_blank style='color:#2F92EE;'>#p53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13627, encryptionId=9d861362e53, topicName=p53)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Sat Nov 04 07:21:00 CST 2017, time=2017-11-04, status=1, ipAttribution=)]
    2017-11-04 zhishijing

    #p53#

    0