Inhibition of v-Abl transformation by p53 and p19ARF

被引:33
|
作者
Cong, F
Zou, XM
Hinrichs, K
Calame, K
Goff, SP
机构
[1] Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA
[2] Columbia Univ, Dept Biol Sci, New York, NY 10025 USA
[3] Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA
[4] Columbia Univ Coll Phys & Surg, Howard Hughes Med Inst, New York, NY 10032 USA
关键词
v-Abl; p53; p19ARF; transformation;
D O I
10.1038/sj.onc.1203290
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tumorigenesis is a multistep process that involves the activation of oncogenes and the inactivation of tumor suppressor genes. The transforming activity of the v-Abl oncogene of Abelson murine leukemia virus (A-MuLV) in immortal cell lines has been well studied, while the effects of v-Abl in primary fibroblasts are less clear. Here we show that v-Abl causes cell cycle arrest in primary mouse embryonic fibroblasts (MEFs) and elevated levels of both p53 and the cyclin-dependent kinase inhibitor p21(Cip). p53(-/-) or p19ARF(-/-) MEFs were resistant to v-Abl-induced cell cycle arrest. Although wild-type MEFs were resistant to v-Abl transforming activity, p53(-/-) or p19ARF(-/-) MEFs were susceptible. The results indicate that loss of p19ARF and p53 function plays an important role during the transformation of primary cells by v-Abl. We suggest that although v-Abl is a potent oncogene, its full potential transforming activity cannot be realized until the ARF-, and p53-dependent growth inhibitory pathway is disabled. We also show that p53 is not the mediator of v-Abl toxicity in immortal fibroblasts and does not determine the susceptibility of immortal fibroblasts to v-Abl transformation.
引用
收藏
页码:7731 / 7739
页数:9
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