Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27Kip1 and p21Cip1
Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27Kip1 and p21Cip1
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DOI：
10.1016/j.ccr.2005.05.006
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发表时间：
2005-06-01
期刊：
影响因子：
50.3
通讯作者：
Barbacid, M
中科院分区：
文献类型：
--
作者：
Martín, A;Odajima, J;Barbacid, M
p27（Kip 1）和p21（Cip 1）被认为通过抑制Cdk 2-cyclin E/A激酶来抑制肿瘤生长和阻止细胞周期进展。由于Cdk 2是有丝分裂细胞分裂的抑制剂，我们分析了这些抑制剂在Cdk 2缺陷细胞中的活性。p27（Kip 1）或p21（Cip 1）的异位表达有效地抑制Cdk 2（-/-）成纤维细胞的细胞周期进程。p27（Kip 1）或p21（Cip 1）的缺失赋予Cdk 2（+/+）和Cdk 2（-/-）细胞类似的增殖优势。此外，Cdk 2是P21（Cip 1）诱导的DNA损伤后细胞周期阻滞的抑制剂。最后，在p2（Kip 1）null小鼠中消融Cdk 2并不能抑制其表型缺陷，包括垂体瘤的发生。这些结果表明Cdk 2不是p27（Kip 1）和p21（Cip 1）在细胞周期抑制和肿瘤抑制中的重要靶点。
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 p2(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.