Rieckhof G E, Casares F, Ryoo H D, Abu-Shaar M, Mann R S
Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Cell. 1997 Oct 17;91(2):171-83. doi: 10.1016/s0092-8674(00)80400-6.
We show that homothorax (hth) is required for the Hox genes to pattern the body of the fruit fly, Drosophila melanogaster. hth is necessary for the nuclear localization of an essential HOX cofactor, Extradenticle (EXD), and encodes a homeodomain protein that shares extensive identity with the product of Meis1, a murine proto-oncogene. MEIS1 is able to rescue hth mutant phenotypes and can induce the cytoplasmic-to-nuclear translocation of EXD in cell culture and Drosophila embryos. Thus, Meis1 is a murine homolog of hth. MEIS1/HTH also specifically binds to EXD with high affinity in vitro. These data suggest a novel and evolutionarily conserved mechanism for regulating HOX activity in which a direct protein-protein interaction between EXD and HTH results in EXD's nuclear translocation.
我们发现，果蝇黑腹果蝇身体模式形成过程中，同源胸节基因（hth）对于Hox基因是必需的。hth对于一种关键的HOX辅因子——额外触角蛋白（EXD）的核定位是必需的，并且编码一种与小鼠原癌基因Meis1的产物具有广泛同源性的同源结构域蛋白。MEIS1能够挽救hth突变体表型，并且在细胞培养和果蝇胚胎中能够诱导EXD从细胞质向细胞核的转运。因此，Meis1是hth的小鼠同源物。MEIS1/HTH在体外也能以高亲和力特异性结合EXD。这些数据提示了一种调控HOX活性的新的、进化上保守的机制，即EXD与HTH之间直接的蛋白质-蛋白质相互作用导致EXD的核转运。
