Ahmed Y, Hayashi S, Levine A, Wieschaus E
Department of Molecular Biology, Princeton University, New Jersey 08544, USA.
Cell. 1998 Jun 26;93(7):1171-82. doi: 10.1016/s0092-8674(00)81461-0.
We find that inactivation of a Drosophila homolog of the tumor suppressor APC (D-APC) causes retinal neuronal degeneration and pigment cell hypertrophy, a phenotype remarkably similar to that found in humans with germline APC mutations. Retinal degeneration in the D-APC mutant results from apoptotic cell death, which accompanies a defect in neuronal differentiation. Reduction in the Drosophila beta-catenin, Armadillo (Arm), rescues the differentiation defect and prevents apoptosis in the D-APC mutant, while Arm overexpression mimics D-APC inactivation. A mutation in dTCF, the DNA-binding protein required in Arm-mediated signal transduction, can eliminate the cell death without rescuing the differentiation defect in D-APC mutants. Uncoupling of these two Arm-induced processes suggests a novel role for the Arm/dTCF complex in the activation of apoptosis.
我们发现，肿瘤抑制因子APC（D - APC）的果蝇同源物失活会导致视网膜神经元变性和色素细胞肥大，该表型与携带种系APC突变的人类患者中发现的表型极为相似。D - APC突变体中的视网膜变性是由凋亡性细胞死亡引起的，这伴随着神经元分化缺陷。果蝇β - 连环蛋白犰狳（Arm）水平的降低挽救了分化缺陷，并防止了D - APC突变体中的细胞凋亡，而Arm的过表达则模拟了D - APC失活。dTCF（Arm介导的信号转导中所需的DNA结合蛋白）的突变可以消除细胞死亡，但不能挽救D - APC突变体中的分化缺陷。这两个由Arm诱导的过程的解偶联表明，Arm/dTCF复合物在细胞凋亡激活中具有新作用。
