Smads bind directly to the Jun family of AP-1 transcription factors
Smads bind directly to the Jun family of AP-1 transcription factors
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DOI：
10.1073/pnas.96.9.4844
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发表时间：
1999-04-27
影响因子：
11.1
通讯作者：
Wang, XF
中科院分区：
文献类型：
--
作者：
Liberati, NT;Datto, MB;Wang, XF
Smad 3和Smad 4是序列特异性DNA结合因子，其响应于转化生长因子β（TGF β）而结合至其共有DNA结合位点并激活转录。最近的证据表明Smad 3和Smad 4在转录激活的共识AP-1 DNA结合位点，不直接与Smads相互作用。在这里，我们报告说，Smad 3和Smad 4可以与AP-1家族成员的物理相互作用。体外结合研究表明，Smad 3和Smad 4都结合所有三个Jun家族成员：JunB、cJun和JunD，JunB的Smad相互作用区域映射到在cJun和JunD中部分保守的C末端20个氨基酸序列。我们表明Smad 3和Smad 4也与响应于TGF β而快速磷酸化的内源形式的cJun相关，Smad和Jun蛋白之间的这种相互作用的重要性提供的证据，我们证明，Smad 3是必需的报告构建体，其特征在于不能直接结合Smad蛋白的多联体AP-1位点的激活。总之，这些数据表明，TGF β介导的转录激活通过AP-1网站可能涉及Smads和AP-1转录因子之间的相互作用的调节。
Smad3 and Smad4 are sequence-specific DNA-binding factors that bind to their consensus DNA-binding sites in response to transforming growth factor beta (TGF beta) and activate transcription. Recent evidence implicates Smad3 and Smad4 in the transcriptional activation of consensus AP-1 DNA-binding sites that do not interact with Smads directly. Here, we report that Smad3 and Smad4 can physically interact with AP-1 family members. In vitro binding studies demonstrate that both Smad3 and Smad4 bind all three Jun family members: JunB, cJun, and JunD, The Smad interacting region of JunB maps to a C-terminal 20-amino acid sequence that is partially conserved in cJun and JunD, We show that Smad3 and Smad4 also associate with an endogenous form of cJun that is rapidly phosphorylated in response to TGF beta, Providing evidence for the importance of this interaction between Smad and Jun proteins, we demonstrate that Smad3 is required for the activation of concatamerized AP-1 sites in a reporter construct that has previously been characterized as unable to bind Smad proteins directly. Together, these data suggest that TGF beta-mediated transcriptional activation through AP-1 sites may involve a regulated interaction between Smads and AP-1 transcription factors.