p21CIP1 is dispensable for the G2 arrest caused by genistein in human melanoma cells
p21CIP1 is dispensable for the G2 arrest caused by genistein in human melanoma cells
复制标题
DOI：
10.1006/excr.2000.4914
复制
发表时间：
2000-07-10
影响因子：
3.7
通讯作者：
Darbon, JM
中科院分区：
文献类型：
--
作者：
Casagrande, F;Darbon, JM
我们研究了金雀异黄素对人脉络膜黑色素瘤细胞系 OCM-1 细胞周期分布的影响。我们报告说，这种异黄酮类化合物可将细胞阻滞在 G2 期。这种效应与 CDK 抑制剂 p21 (CIP1) 的诱导相关。然而，虽然金雀异黄素治疗后 CDK1 活性显着降低，但 CDK2 活性并未受到影响。这与我们观察到的 G1 停滞不存在一致，但引起了对 p21(CIP1) 功能的一些怀疑。证明 OCM-1 细胞 p21(CIP1) 突变或翻译后修饰的尝试未成功。事实上，金雀异黄素诱导的 p21(CIP1) 水平不足以引起 CDK2 抑制。 p21(CIP1) 在抑制 CDK1 中的作用值得怀疑，因为我们证明金雀异黄素会损害 CDK1 的 Tyr15 去磷酸化，并且因为处理细胞中的 CDK1-细胞周期蛋白 B1 复合物在暴露于 CDC25 磷酸酶后可能会重新激活。 pal 缺陷的 Rat-1 成纤维细胞与 p21-/- 小鼠胚胎成纤维细胞一样呈网状。 (C) 2000 年学术出版社。
We have investigated the effect of genistein on cell cycle distribution of the human choroidal melanoma cell line OCM-1. We report that this isoflavonoid arrested cells in G2. This effect was correlated with the induction of the CDK inhibitor p21(CIP1). However, while CDK1 activity was markedly reduced following genistein treatment, CDK2 activity was not affected. This was in agreement with the absence of G1 arrest that we observed but caused some doubt about the functionality of p21(CIP1). Attempts to demonstrate mutation or post-translational modification of p21(CIP1) from OCM-1 cells were unsuccessful. In fact, the level of p21(CIP1) induced by genistein was shown to be unsufficient to cause CDK2 inhibition. The role of p21(CIP1) in the inhibition of CDK1 was questionable, as we demonstrated that genistein impaired Tyr15 dephosphorylation of CDK1 and because CDK1-cyclin B1 complexes from treated cells could be reactivated upon exposure to CDC25 phosphatase, Finally, we report that p21(CIP1) was not absolutely required for the genistein-induced G2 arrest, as the isoflavone caused at least partial G2 arrest in pal-deficient Rat-1 fibroblasts as web as in p21-/- mouse embryo fibroblasts. (C) 2000 Academic Press.