An autoinhibitory effect of the homothorax domain of Meis2.
An autoinhibitory effect of the homothorax domain of Meis2.
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Meis2 同胸结构域的自抑制作用。
DOI：
10.1111/j.1742-464x.2010.07668.x
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Wotton,David
中科院分区：
文献类型：
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作者：
Hyman-Walsh,Cathy;Bjerke,GlenA;Wotton,David
髓样嗜亲性插入位点2（Myeloid ecotropic insertion site，Meis）2是一个同源结构域蛋白，含有一个保守的同型胸（homothorax，Hth）结构域，该结构域存在于所有Meis和Prep家族蛋白以及果蝇Hth蛋白中。Hth结构域介导与Pbx同源结构域蛋白的相互作用，允许有效的DNA结合。在这里，我们表明，像Meis 1，Meis 2有一个强大的C末端转录激活结构域，这是由Meis 2和Pbx 1组成的同源结构域蛋白复合物完全激活转录所必需的。我们还表明，激活结构域的活性被抑制的Hth域，这种自抑制可以部分缓解Pbx 1与Hth域的Meis 2的相互作用。Hth结构域靶向DNA表明它不是一个可移植的反式作用抑制结构域。然而，Hth结构域可以抑制连接的激活结构域，并且这种抑制不限于Meis 2激活结构域。数据库搜索显示，在几种脊椎动物中发现的Meis3.2剪接变体通过从外显子6的5′端移除17个密码子来破坏Hth结构域。 我们发现Meis 2中的等同缺失解除了C末端激活结构域的抑制，并减弱了与Pbx 1的相互作用。这项工作表明，Meis/Prep Hth蛋白家族的所有成员的转录活性都受到Hth结构域的自抑制，而Meis 3.2剪接变体编码的蛋白质绕过了这种自抑制效应。结构化数字摘要·MINT-7718353，MINT-7718083，MINT-7718172，MINT-7718256，MINT-7718300，MINT-7718330：Meis 2d（uniprotkb：O 14770 - 4）通过抗标签免疫共沉淀（MI：0007）与PBX 1（uniprotkb：P40424）物理相互作用（MI：0915）·MINT-7718110：Meis 2 e（uniprotkb：O 14770 - 5）通过抗标签免疫共沉淀（MI：0007）与PBX 1（uniprotkb：P40424）物理相互作用（MI：0915）
Myeloid ecotropic insertion site (Meis)2 is a homeodomain protein containing a conserved homothorax (Hth) domain that is present in all Meis and Prep family proteins and in theDrosophilaHth protein. The Hth domain mediates interaction with Pbx homeodomain proteins, allowing for efficient DNA binding. Here we show that, like Meis1, Meis2 has a strong C‐terminal transcriptional activation domain, which is required for full activation of transcription by homeodomain protein complexes composed of Meis2 and Pbx1. We also show that the activity of the activation domain is inhibited by the Hth domain, and that this autoinhibition can be partially relieved by the interaction of Pbx1 with the Hth domain of Meis2. Targeting of the Hth domain to DNA suggests that it is not a portable trans‐acting repression domain. However, the Hth domain can inhibit a linked activation domain, and this inhibition is not limited to the Meis2 activation domain. Database searching reveals that theMeis3.2splice variant, which is found in several vertebrate species, disrupts the Hth domain by removing 17 codons from the 5′‐end of exon 6. We show that the equivalent deletion in Meis2 derepresses the C‐terminal activation domain and weakens interaction with Pbx1. This work suggests that the transcriptional activity of all members of the Meis/Prep Hth protein family is subject to autoinhibition by their Hth domains, and that theMeis3.2splice variant encodes a protein that bypasses this autoinhibitory effect.Structured digital abstract•MINT‐7718353, MINT‐7718083, MINT‐7718172, MINT‐7718256, MINT‐7718300, MINT‐7718330:Meis2d(uniprotkb:O14770‐4)physically interacts(MI:0915) withPBX1(uniprotkb:P40424) byanti tag coimmunoprecipitation(MI:0007)•MINT‐7718110:Meis2e(uniprotkb:O14770‐5)physically interacts(MI:0915) withPBX1(uniprotkb:P40424) byanti tag coimmunoprecipitation(MI:0007)