KIS induces proliferation and the cell cycle progression through the phosphorylation of p27Kip1 in leukemia cells
KIS induces proliferation and the cell cycle progression through the phosphorylation of p27Kip1 in leukemia cells
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DOI：
10.1016/j.leukres.2008.02.012
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发表时间：
2008-09-01
影响因子：
2.7
通讯作者：
Ohnishi, Kazunori
中科院分区：
文献类型：
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作者：
Nakamura, Satoki;Okinaka, Keiji;Ohnishi, Kazunori
用慢病毒介导的siRNA KIS基因转导CEM、MOLT 4和SUP-B15细胞。KIS的mRNA表达在所有细胞系中均被成功地降低。转染siRNA KIS基因后，CEM、MOLT 4和SUP-B15细胞中p27（Kip 1）mRNA的表达无明显变化。我们发现KIS蛋白直接与p27（Kip 1）蛋白相互作用，并且KIS的减少抑制白血病细胞中p27（Kip 1）的S10磷酸化。在这些细胞转染siRNA KIS，抑制S10磷酸化的p27（Kip 1）强烈抑制细胞增殖的时间依赖性的方式。此外，抑制S10磷酸化的p27（Kip 1）增加了显着的人口在G 0/G1级分。这些数据表明KIS活性在G 0/G1期间被诱导，并且它通过磷酸化p27上的S10（Kip 1）来促进细胞周期进程。我们发现，在原发性白血病标本中，37例，骨髓增生异常综合征（MDS）; 72例，急性淋巴细胞白血病（ALL）; AML、MDS和ALL标本中KIS与G3 PDH的平均比值分别为3.62 ± 0.68、3.27 ± 0.73和3.17 ± 0.58。132例成人白血病中，包括37例AML（8例M1，12例M2，2例M3，7例M4，8例M5），72例MDS（42例RAEB-I，30例REAB-II），23例ALL（23例L2），KIS蛋白均呈高表达。本研究表明，白血病细胞中KIS蛋白水平的升高促进了白血病细胞的细胞周期进程。(C)2008爱思唯尔有限公司保留所有权利。
CEM, MOLT4 and SUP-B15 cells were transduced with lentivirus-mediated siRNA KIS gene. The mRNA expressions of KIS were successfully reduced in all cell lines. On the other hand, the mRNA expressions of p27(Kip1) in CEM, MOLT4 and SUP-B15 cells were not affected by the transduction with siRNA KIS gene. We showed that KIS protein directly interacted with p27(Kip1), protein, and reduction of KIS inhibited the S10 phosphorylation of p27(Kip1) in leukemia cells. On these cells transfected with siRNA KIS, the inhibition of S10 phosphorylation of p27(Kip1) was strongly suppressed cell proliferation in a time-dependent manner. Moreover, the inhibition of S10 phosphorylation of p27(Kip1) increased a significant population in G0/G1 fraction. These data demonstrated that the KIS activity was induced during G0/G1, and it promotes cell cycle progression by phosphorylation of S10 on p27(Kip1). We showed that KIS mRNA expression was increased in primary leukemia specimens (acute myelogenous leukemia (AML); 37, myelodysplastic syndrome (MDS); 72, acute lymphoblastic leukemia (ALL); 23), and the mean ratios of KIS to G3PDH in AML, MDS and ALL specimens were 3.62 +/- 0.68, 3.27 +/- 0.73 and 3.17 +/- 0.58, respectively. Moreover, we found that KIS protein was overexpressed in all 132 adults cases of various leukemias, including 37 AML (8 M1, 12 M2, 2 M3, 7 M4, 8 M5), 72 MDS (42 RAEB-I, 30 REAB-II) and 23 ALL (23 L2). This study demonstrates that the elevated levels of KIS protein in leukemia cells promote the cell cycle progression in leukemia cells. (C) 2008 Elsevier Ltd. All rights reserved.