van Meyel D J, O'Keefe D D, Jurata L W, Thor S, Gill G N, Thomas J B
Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Mol Cell. 1999 Aug;4(2):259-65. doi: 10.1016/s1097-2765(00)80373-1.
LIM homeodomain (LIM-HD) proteins play key roles in a variety of developmental processes throughout the animal kingdom. Here we show that the LIM-binding protein Chip acts as a cofactor for the Drosophila LIM-HD family member Apterous (Ap) in wing development. We define the domains of Chip required for LIM-HD binding and for homodimerization and show that mutant proteins deleted for these domains act in a dominant-negative fashion to disrupt Ap function. Our results support a model for multimeric complexes containing Chip and Ap in transcriptional regulation. This model is confirmed by the activity of a chimeric fusion between Chip and Ap that reconstitutes the complex and rescues the ap mutant phenotype.
LIM 同源结构域(LIM-HD)蛋白在整个动物界的各种发育过程中发挥着关键作用。在此我们表明,LIM 结合蛋白 Chip 在翅膀发育过程中作为果蝇 LIM-HD 家族成员无翅(Ap)的辅因子发挥作用。我们确定了 Chip 与 LIM-HD 结合以及同源二聚化所需的结构域,并表明缺失这些结构域的突变蛋白以显性负性方式发挥作用,破坏 Ap 的功能。我们的结果支持了在转录调控中含有 Chip 和 Ap 的多聚体复合物的模型。Chip 和 Ap 之间的嵌合融合体的活性证实了该模型,该融合体重构了复合物并挽救了 ap 突变体表型。