Milán M, Diaz-Benjumea F J, Cohen S M
European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Genes Dev. 1998 Sep 15;12(18):2912-20. doi: 10.1101/gad.12.18.2912.
Formation of the dorsal-ventral axis of the Drosophila wing depends on activity of the LIM-homeodomain protein Apterous (Ap). Here we report that Ap activity levels are modulated by dLMO, the protein encoded by the Beadex (Bx) gene. Overexpression of dLMO in Bx mutants interferes with Apterous function. Conversely, Bx loss-of-function mutants fail to down-regulate Apterous activity at late stages of wing development. Biochemical analysis shows that dLMO protein competes for binding of Apterous to its cofactor Chip. These data suggest that Apterous activity depends on formation of a functional complex with Chip and that the relative levels of dLMO, Apterous, and Chip determine the level of Apterous activity. The dominant interference mechanism of dLMO action may serve as a model for the mechanism by which LMO oncogenes cause cancer when misexpressed in T cells.
果蝇翅膀背腹轴的形成依赖于LIM同源域蛋白无翅(Ap)的活性。我们在此报告,Ap的活性水平受Beadex(Bx)基因编码的蛋白dLMO调节。在Bx突变体中过表达dLMO会干扰无翅功能。相反,Bx功能丧失突变体在翅膀发育后期无法下调无翅活性。生化分析表明,dLMO蛋白竞争无翅与辅因子Chip的结合。这些数据表明,无翅活性依赖于与Chip形成功能性复合物,且dLMO、无翅和Chip的相对水平决定了无翅活性的水平。dLMO作用的显性干扰机制可能为LMO癌基因在T细胞中错误表达时导致癌症的机制提供一个模型。