Kataoka K, Yoshitomo-Nakagawa K, Shioda S, Nishizawa M
Department of Virology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku 108-8639, Tokyo, Japan.
J Biol Chem. 2001 Jan 5;276(1):819-26. doi: 10.1074/jbc.M007643200.
Maf oncoprotein is a basic-leucine zipper (bZip) type of transcriptional activator. Since many transcription factors are known to form functional complexes, we searched for proteins that interact with the DNA-binding domain of Maf using the phage display method and identified two homeodomain-containing proteins, Hoxd12 and MHox/Prx1/Phox1/Pmx1. Studies with mutants of Hox and Maf proteins showed that they associate through their DNA-binding domains; the homeodomain of Hox and the bZip domain of Maf, respectively. Reflecting the high similarity of the bZip domain, all other Maf family members tested (c-/v-Maf, MafB, MafK, MafF, and MafG) also associated with the Hox proteins. Pax6, whose homeodomain is relatively similar to MHox, also could interact with Maf. However, two other bZip oncoproteins, Fos and Jun, failed to associate with the Hox proteins, while a distantly related Hox family member, Meis1, could not interact with Maf. Through interactions with the bZip domain, the Hox proteins inhibited the DNA binding activity of Maf, whereas the binding of Hox proteins to their recognition sequences was not abrogated by Maf. We further showed that coexpression of the Hox proteins repressed transcriptional activation and transforming activity of Maf. These results suggested that the interaction of a set of Hox proteins with Maf family members may interfere not only with their oncogenicity but also with their physiological roles.
Maf原癌蛋白是一种碱性亮氨酸拉链（bZip）型转录激活因子。由于已知许多转录因子会形成功能复合物，我们利用噬菌体展示法寻找与Maf的DNA结合域相互作用的蛋白质，并鉴定出两种含同源异型结构域的蛋白质，即Hoxd12和MHox/Prx1/Phox1/Pmx1。对Hox和Maf蛋白突变体的研究表明，它们通过各自的DNA结合域相互关联，分别是Hox的同源异型结构域和Maf的bZip结构域。由于bZip结构域具有高度相似性，所有其他测试的Maf家族成员（c-/v-Maf、MafB、MafK、MafF和MafG）也与Hox蛋白相关联。Pax6的同源异型结构域与MHox相对相似，也能与Maf相互作用。然而，另外两种bZip原癌蛋白Fos和Jun未能与Hox蛋白相关联，而一个远亲的Hox家族成员Meis1则不能与Maf相互作用。通过与bZip结构域的相互作用，Hox蛋白抑制了Maf的DNA结合活性，而Maf并未消除Hox蛋白与其识别序列的结合。我们进一步表明，Hox蛋白的共表达抑制了Maf的转录激活和转化活性。这些结果表明，一组Hox蛋白与Maf家族成员的相互作用可能不仅会干扰它们的致癌性，还会干扰它们的生理作用。
