Activation of the TGF-ýý/Smad signaling pathway in oncogenic transformation by v-Rel.
Activation of the TGF-ýý/Smad signaling pathway in oncogenic transformation by v-Rel.
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v-Rel 激活致癌转化中的 TGF-α/Smad 信号通路。
DOI：
10.1016/j.virol.2011.02.002
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
BoseJr,HenryR
中科院分区：
文献类型：
--
作者：
Tiwari,Richa;Bargmann,William;BoseJr,HenryR
v-rel是禽网状内皮组织增生病病毒（avian reticuloendotheliosis virus，AVV）编码的一种转录因子，属于Rel/NF-κB家族，具有急性转化功能。通过v-Rel的转化由通常由Rel/NF-κB调节的基因的异常表达介导。在这里，我们证明了TGF-β/Smad信号通路在Rel转化中的激活。关键TGF-β和Smad家族成员（TGF-β2、TGF-β3、TGF-β II型受体和Smad 3）的RNA和蛋白质水平在v-Rel转化细胞中上调，而在c-Rel表达细胞中几乎没有变化。用TGF-β受体的激酶抑制剂处理v-Rel转化的淋巴样细胞显著减少软琼脂集落形成，而加入TGF-β2进一步促进转化。此外，Smad 3而不是Smad 2被选择性地激活为TGF-β信号传导的下游介导物。阻断Smad 3表达或活性抑制v-Rel的致癌潜力。总体而言，TGF-β/Smad信号传导在多个水平上被激活，并且是v-Rel的转化能力所需的。
v-rel, encoded by the avian reticuloendotheliosis virus, is an acutely transforming member of the Rel/NF-κB family of transcription factors. Transformation by v-Rel is mediated by the aberrant expression of genes that are normally regulated by Rel/NF-κB. Here, we demonstrate activation of the TGF-β/Smad signaling pathway in Rel transformation. RNA and protein levels of key TGF-β and Smad family members (TGF-β2, -β3, TGF-β type II receptor, and Smad3) are upregulated in v-Rel transformed cells with little to no change in c-Rel-expressing cells. Treatment of v-Rel transformed lymphoid cells with kinase inhibitors of the TGF-β receptor dramatically reduces soft agar colony formation whereas addition of TGF-β2 further promotes transformation. Moreover, Smad3 but not Smad2, is selectively activated as the downstream mediator of TGF-β signaling. Blocking Smad3 expression or activity inhibits the oncogenic potential of v-Rel. Overall, TGF-β/Smad signaling is activated at multiple levels and is required for the transforming ability of v-Rel.