Martín Alberto, Odajima Junko, Hunt Sarah L, Dubus Pierre, Ortega Sagrario, Malumbres Marcos, Barbacid Mariano
Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Cancer Cell. 2005 Jun;7(6):591-8. doi: 10.1016/j.ccr.2005.05.006.
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.
p27（Kip1）和p21（Cip1）被认为通过抑制Cdk2-细胞周期蛋白E/A激酶来抑制肿瘤生长并阻止细胞周期进程。由于Cdk2对于有丝分裂细胞分裂并非必需，我们分析了这些抑制剂在Cdk2缺陷细胞中的活性。p27（Kip1）或p21（Cip1）的异位表达有效抑制了Cdk2（-/-）成纤维细胞的细胞周期进程。p27（Kip1）或p21（Cip1）的缺失赋予Cdk2（+/+）和Cdk2（-/-）细胞相似的增殖优势。此外，DNA损伤后，Cdk2对于p21（Cip1）诱导的细胞周期停滞并非必需。最后，在p27（Kip1）基因敲除小鼠中敲除Cdk2并不能抑制其表型缺陷，包括垂体肿瘤的发生。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）的必需靶点。
