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J CELL SCI：动物所揭示细胞核内Net1调控TGF-β信号转导机制

2017-08-11 动物所 动物所

动物所细胞核Net1TGF-β信号转导机制
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Nodal是TGF-β超家族成员之一，在脊椎动物胚胎中内胚层诱导、神经图式形成、原肠运动、内脏器官左右不对称等发育过程中具有广泛而重要的作用。中国科学院动物研究所研究员王强领导的研究组主要从事TGF-β家族跨膜信号转导通路在胚胎早期发育及组织器官形成中的调控机制研究。他们在原肠期斑马鱼胚胎中系统鉴定了Nodal/Smad2信号的靶基因，其中包括鸟核苷酸交换因子Net1（J Biol Chem. 2

Nodal是TGF-β超家族成员之一，在脊椎动物胚胎中内胚层诱导、神经图式形成、原肠运动、内脏器官左右不对称等发育过程中具有广泛而重要的作用。中国科学院动物研究所研究员王强领导的研究组主要从事TGF-β家族跨膜信号转导通路在胚胎早期发育及组织器官形成中的调控机制研究。他们在原肠期斑马鱼胚胎中系统鉴定了Nodal/Smad2信号的靶基因，其中包括鸟核苷酸交换因子Net1（J Biol Chem. 2011）。Net1蛋白主要位于细胞核，少量位于细胞质，在多种肿瘤细胞中高表达，通过激活小G蛋白RhoA促进肿瘤细胞侵袭和转移。王强研究组的前期研究发现，斑马鱼的net1是MBT前后最早表达的合子基因之一，特异表达于预定背部组织中心。Net1通过激活RhoA家族的G蛋白，干扰PAK1二聚体的形成，激活PAK1激酶活性，从而磷酸化β-catenin 675位丝氨酸，抑制β-catenin与组蛋白去乙酰化酶HDAC结合，促进Wnt靶基因转录，在胚胎背部轴建立过程中发挥重要作用（Cell Research. 2017）。然而，目前对于细胞核内Net1的功能还所知甚少。

TGF-β/Nodal靶基因可以反馈调控信号通路。例如TGF-β信号通路激活2小时，可以显着增加SnoN的转录；另一方面，SnoN可以抑制Smad2及Smad3的磷酸化及Smad复合体与DNA结合，是TGF-β信号通路的抑制因子。因此，作为TGF-β/Nodal信号通路的靶基因，Net1可能参与了TGF-β信号通路的调控。王强研究组的研究发现，在胚胎及哺乳动物细胞中敲低net1后，抑制了TGF-β/Nodal信号活性，致使中内胚层及其衍生器官的形成产生严重缺陷。进一步的研究表明，与Net1鸟核苷酸交换因子活性无关，定位于细胞核内的Net1通过与Smad2结合，增强Smad2招募组蛋白乙酰化酶p300的能力，促进胚胎中内胚层的形成。因此，在脊椎动物早期胚胎发育过程中，Net1分别作为鸟核苷酸交换因子和适配体蛋白，整合了Wnt/β-catenin和Nodal/Smad2两种极为重要的信号通路，在体轴建立和中内胚层形成过程中扮演了关键的角色。鉴于TGF-β、Wnt及Net1在肿瘤细胞增殖、侵袭和转移中的重要作用，这项研究结果还为了解相关肿瘤发生发展机制及肿瘤诊治方面开拓了新的思路。

这项研究工作以A GEF activity-independent function for nuclear Net1 in Nodal/Smad2 signal transduction and mesendoderm formation 为题于8月4日在《细胞科学杂志》（Journal of Cell Science）在线发表。中科院动物所博士魏奭为该论文第一作者，王强为通讯作者。该研究得到了国家重点研发计划和国家自然科学基金的资助。

原始出处：
Wei S, Ning G, Li L, Yan Y, Yang S, Cao Y, Wang Q.A GEF activity-independent function for nuclear Net1 in Nodal/Smad2 signal transduction and mesendoderm formation.J Cell Sci. 2017 Aug 4. pii: jcs.204917. doi: 10.1242/jcs.204917.

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    2018-03-10 维他命

    #CEL#

    0

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    2018-05-17 changhe713

    #TGF#

    0

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    2018-01-23 zhaozhouchifen

    #Cell#

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    2018-06-13 canlab

    #NET#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1960371, encodeId=23c919603e195, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Mar 10 12:59:00 CST 2018, time=2018-03-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2035851, encodeId=c70b203585193, content=<a href='/topic/show?id=575c1e341a8' target=_blank style='color:#2F92EE;'>#TGF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17341, encryptionId=575c1e341a8, topicName=TGF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=56ea361, createdName=changhe713, createdTime=Thu May 17 02:59:00 CST 2018, time=2018-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870111, encodeId=009f18e011186, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Jan 23 06:59:00 CST 2018, time=2018-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733911, encodeId=da251e339116e, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Wed Jun 13 03:59:00 CST 2018, time=2018-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813627, encodeId=36c5181362e25, content=<a href='/topic/show?id=9bbe933362a' target=_blank style='color:#2F92EE;'>#转导机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93336, encryptionId=9bbe933362a, topicName=转导机制)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/72D57F5B3E12B2BB53D6BD015D14DCD6/100, createdBy=a92e2500162, createdName=passed water, createdTime=Wed Nov 22 02:59:00 CST 2017, time=2017-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441355, encodeId=ee6514413559e, content=<a href='/topic/show?id=58dd1e34591' target=_blank style='color:#2F92EE;'>#TGF-β#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17345, encryptionId=58dd1e34591, topicName=TGF-β)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sun Aug 13 12:59:00 CST 2017, time=2017-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603598, encodeId=42171603598bc, content=<a href='/topic/show?id=3831e7930d9' target=_blank style='color:#2F92EE;'>#细胞核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77930, encryptionId=3831e7930d9, topicName=细胞核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=52c219056124, createdName=ying_wu, createdTime=Sun Aug 13 12:59:00 CST 2017, time=2017-08-13, status=1, ipAttribution=)]
    2017-11-22 passed water

    #转导机制#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1960371, encodeId=23c919603e195, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Mar 10 12:59:00 CST 2018, time=2018-03-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2035851, encodeId=c70b203585193, content=<a href='/topic/show?id=575c1e341a8' target=_blank style='color:#2F92EE;'>#TGF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17341, encryptionId=575c1e341a8, topicName=TGF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=56ea361, createdName=changhe713, createdTime=Thu May 17 02:59:00 CST 2018, time=2018-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870111, encodeId=009f18e011186, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Jan 23 06:59:00 CST 2018, time=2018-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733911, encodeId=da251e339116e, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Wed Jun 13 03:59:00 CST 2018, time=2018-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813627, encodeId=36c5181362e25, content=<a href='/topic/show?id=9bbe933362a' target=_blank style='color:#2F92EE;'>#转导机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93336, encryptionId=9bbe933362a, topicName=转导机制)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/72D57F5B3E12B2BB53D6BD015D14DCD6/100, createdBy=a92e2500162, createdName=passed water, createdTime=Wed Nov 22 02:59:00 CST 2017, time=2017-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441355, encodeId=ee6514413559e, content=<a href='/topic/show?id=58dd1e34591' target=_blank style='color:#2F92EE;'>#TGF-β#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17345, encryptionId=58dd1e34591, topicName=TGF-β)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sun Aug 13 12:59:00 CST 2017, time=2017-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603598, encodeId=42171603598bc, content=<a href='/topic/show?id=3831e7930d9' target=_blank style='color:#2F92EE;'>#细胞核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77930, encryptionId=3831e7930d9, topicName=细胞核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=52c219056124, createdName=ying_wu, createdTime=Sun Aug 13 12:59:00 CST 2017, time=2017-08-13, status=1, ipAttribution=)]
    2017-08-13 zhaojie88

    #TGF-β#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1960371, encodeId=23c919603e195, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Mar 10 12:59:00 CST 2018, time=2018-03-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2035851, encodeId=c70b203585193, content=<a href='/topic/show?id=575c1e341a8' target=_blank style='color:#2F92EE;'>#TGF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17341, encryptionId=575c1e341a8, topicName=TGF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=56ea361, createdName=changhe713, createdTime=Thu May 17 02:59:00 CST 2018, time=2018-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870111, encodeId=009f18e011186, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Jan 23 06:59:00 CST 2018, time=2018-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1733911, encodeId=da251e339116e, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Wed Jun 13 03:59:00 CST 2018, time=2018-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813627, encodeId=36c5181362e25, content=<a href='/topic/show?id=9bbe933362a' target=_blank style='color:#2F92EE;'>#转导机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93336, encryptionId=9bbe933362a, topicName=转导机制)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/72D57F5B3E12B2BB53D6BD015D14DCD6/100, createdBy=a92e2500162, createdName=passed water, createdTime=Wed Nov 22 02:59:00 CST 2017, time=2017-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441355, encodeId=ee6514413559e, content=<a href='/topic/show?id=58dd1e34591' target=_blank style='color:#2F92EE;'>#TGF-β#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17345, encryptionId=58dd1e34591, topicName=TGF-β)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sun Aug 13 12:59:00 CST 2017, time=2017-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603598, encodeId=42171603598bc, content=<a href='/topic/show?id=3831e7930d9' target=_blank style='color:#2F92EE;'>#细胞核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77930, encryptionId=3831e7930d9, topicName=细胞核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=52c219056124, createdName=ying_wu, createdTime=Sun Aug 13 12:59:00 CST 2017, time=2017-08-13, status=1, ipAttribution=)]
    2017-08-13 ying_wu

    #细胞核#

    0

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