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Pim-2 对 p21(Cip1/WAF1)的磷酸化增强了其稳定性，抑制了 HCT116 细胞的增殖。

Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and inhibits cell proliferation in HCT116 cells.

机构信息

School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, USA.

出版信息

Int J Biochem Cell Biol. 2010 Jun;42(6):1030-8. doi: 10.1016/j.biocel.2010.03.012. Epub 2010 Mar 20.

DOI:10.1016/j.biocel.2010.03.012
PMID:20307683
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2862799/
Abstract

Pim-2 kinase is one of the three highly conserved Pim family members which are known to be involved in cell survival and cell proliferation. Here we demonstrate that like Pim-1, Pim-2 also phosphorylates the cell cycle inhibitor p21(Cip1/WAF1) (p21) on Thr145 in vitro and in vivo. Overexpression of Pim-2 in HCT116 cells leads to the increased stability of p21 and results in enhanced levels of both exogenous and endogenous p21 proteins. Knockdown of Pim-2 expression via siRNA results in reduced level of endogenous p21, indicating that like Pim-1, Pim-2 is another legitimate p21 kinase. However, Pim-2 has no influence on the nuclear localization of p21 in HCT116 cells. In addition, Pim-2 is able to arrest the cell cycle at G1/S phase and inhibit cell proliferation through phosphorylation of p21 in HCT116 cells. These data suggest that Pim-2 phosphorylation of p21 enhances p21's stability and inhibits cell proliferation in HCT116 cells.

摘要

Pim-2 激酶是三个高度保守的 Pim 家族成员之一，已知其参与细胞存活和细胞增殖。在这里，我们证明 Pim-2 与 Pim-1 一样，也可在体外和体内将细胞周期抑制剂 p21(Cip1/WAF1)（p21）磷酸化到 Thr145 位。在 HCT116 细胞中过表达 Pim-2 会导致 p21 的稳定性增加，从而导致外源性和内源性 p21 蛋白水平均增强。通过 siRNA 敲低 Pim-2 的表达会导致内源性 p21 水平降低，表明 Pim-2 与 Pim-1 一样，是另一种有效的 p21 激酶。然而，Pim-2 对 HCT116 细胞中 p21 的核定位没有影响。此外，Pim-2 通过在 HCT116 细胞中磷酸化 p21，能够将细胞周期阻滞在 G1/S 期并抑制细胞增殖。这些数据表明，Pim-2 对 p21 的磷酸化增强了 p21 的稳定性并抑制了 HCT116 细胞的增殖。

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