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首页> 外文期刊>Cancer Cell >Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27(Kip1) and p21(Cip1).
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Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27(Kip1) and p21(Cip1).

机译:Cdk2可用于细胞周期抑制和p27(Kip1)和p21(Cip1)介导的肿瘤抑制。

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摘要

p27(Kip1) and p21(Cip1) are thought to suppress tumor growth and prevent cell cycle progression by inhibiting Cdk2-cyclin E/A kinases. Since Cdk2 is dispensable for mitotic cell division, we analyzed the activity of these inhibitors in Cdk2-deficient cells. Ectopic expression of p27(Kip1) or p21(Cip1) efficiently inhibits cell cycle progression of Cdk2(-/-) fibroblasts. Loss of p27(Kip1) or p21(Cip1) confers similar proliferative advantages to Cdk2(+/+) and Cdk2(-/-) cells. Moreover, Cdk2 is dispensable for p21(Cip1)-induced cell cycle arrest after DNA damage. Finally, ablation of Cdk2 in p27(Kip1) null mice does not suppress their phenotypic defects, including development of pituitary tumors. These results indicate that Cdk2 is not an essential target for p27(Kip1) and p21(Cip1) in cell cycle inhibition and tumor suppression.
机译:p27(Kip1)和p21(Cip1)被认为通过抑制Cdk2-cyclin E / A激酶来抑制肿瘤生长并阻止细胞周期进程。由于Cdk2是有丝分裂细胞分裂所必需的,因此我们分析了Cdk2缺陷细胞中这些抑制剂的活性。 p27(Kip1)或p21(Cip1)的异位表达有效抑制Cdk2(-/-)成纤维细胞的细胞周期进程。 p27(Kip1)或p21(Cip1)的丧失赋予Cdk2(+ / +)和Cdk2(-/-)细胞类似的增殖优势。此外,Cdk2可用于DNA损伤后p21(Cip1)诱导的细胞周期停滞。最后,消融p27(Kip1)null小鼠中的Cdk2不能抑制其表型缺陷,包括垂体瘤的发展。这些结果表明在细胞周期抑制和肿瘤抑制中,Cdk2不是p27(Kip1)和p21(Cip1)的必需靶标。

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