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Myc对细胞周期蛋白E-cdk2激酶活性、E2F依赖性转录及细胞生长的诱导是可通过遗传学方法分离的事件。

Induction of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth by Myc are genetically separable events.

作者信息

Beier R, Bürgin A, Kiermaier A, Fero M, Karsunky H, Saffrich R, Möröy T, Ansorge W, Roberts J, Eilers M

机构信息

Institute of Molecular Biology and Tumour Research, Emil-Mannkopff-Strabetae 2, 35033 Marburg, Germany.

出版信息

EMBO J. 2000 Nov 1;19(21):5813-23. doi: 10.1093/emboj/19.21.5813.

Abstract

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.

摘要

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。

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