Beier R, Bürgin A, Kiermaier A, Fero M, Karsunky H, Saffrich R, Möröy T, Ansorge W, Roberts J, Eilers M
Institute of Molecular Biology and Tumour Research, Emil-Mannkopff-Strabetae 2, 35033 Marburg, Germany.
EMBO J. 2000 Nov 1;19(21):5813-23. doi: 10.1093/emboj/19.21.5813.
The c-myc gene has been implicated in three distinct genetic programs regulating cell proliferation: control of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth. We have now used p27(-/-) fibroblasts to dissect these downstream signalling pathways. In these cells, activation of Myc stimulates transcription of E2F target genes, S-phase entry and cell growth without affecting cyclin E-cdk2 kinase activity. Both cyclin D2 and E2F2, potential direct target genes of Myc, are induced in p27(-/-) MycER cells. Ectopic expression of E2F2, but not of cyclin D2, induces S-phase entry, but, in contrast to Myc, does not stimulate cell growth. Our results show that stimulation of cyclin E-cdk2 kinase, of E2F-dependent transcription and of cell growth by Myc can be genetically separated from each other.
c-myc基因与调控细胞增殖的三种不同遗传程序有关：细胞周期蛋白E-cdk2激酶活性的控制、E2F依赖的转录和细胞生长。我们现在利用p27(-/-)成纤维细胞来剖析这些下游信号通路。在这些细胞中，Myc的激活刺激E2F靶基因的转录、进入S期和细胞生长，而不影响细胞周期蛋白E-cdk2激酶活性。细胞周期蛋白D2和E2F2这两个Myc潜在的直接靶基因，在p27(-/-)MycER细胞中均被诱导表达。E2F2的异位表达而非细胞周期蛋白D2的异位表达可诱导细胞进入S期，但与Myc不同的是，它不刺激细胞生长。我们的结果表明，Myc对细胞周期蛋白E-cdk2激酶、E2F依赖的转录和细胞生长的刺激在遗传上是可以相互分离的。
