Increased expression of cyclin D2 during multiple states of growth arrest in primary and established cells
Increased expression of cyclin D2 during multiple states of growth arrest in primary and established cells
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DOI：
10.1128/mcb.18.6.3163
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发表时间：
1998-06-01
影响因子：
5.3
通讯作者：
Riabowol, KT
中科院分区：
文献类型：
--
作者：
Meyyappan, M;Wong, H;Riabowol, KT
细胞周期蛋白D2是D型细胞周期蛋白家族的一员，与细胞周期调节、分化和致癌转化有关。为了更好地理解这种细胞周期蛋白在控制细胞增殖中的作用，在各种生长条件下在原代人和建立的鼠成纤维细胞中监测细胞周期蛋白D2的表达。在接触抑制，血清饥饿，或细胞衰老启动的细胞生长停滞的不同状态下，细胞周期蛋白D2的mRNA和蛋白质的表达水平显着增加（5- 20倍）。间接免疫荧光研究表明，细胞周期蛋白D2蛋白定位于细胞核G（0），表明细胞周期蛋白D2在静止细胞的核功能。还发现细胞周期蛋白D2与细胞周期蛋白依赖性激酶CDK 2和CDK 4相关，但在生长停滞期间与CDK 6无关。细胞周期蛋白D2-CDK 2复合物的数量增加，但在静止细胞中组蛋白H1激酶无活性。细胞周期蛋白D2表达构建体的瞬时转染和针显微注射表明细胞周期蛋白D2蛋白的过表达有效地抑制细胞周期进程和DNA合成。这些数据表明，除了通过在某些细胞系统中视网膜母细胞瘤家族蛋白的磷酸化促进细胞周期进展的作用外，细胞周期蛋白D2可能有助于诱导和/或维持非增殖状态，可能是通过螯合CDK 2催化亚基。
Cyclin D2 is a member of the family of D-type cyclins that is implicated in cell cycle regulation, differentiation, and oncogenic transformation. To better understand the role of this cyclin in the control of cell proliferation, cyclin D2 expression was monitored under various growth conditions in primary human and established murine fibroblasts. In different states of cellular growth arrest initiated by contact inhibition, serum starvation, or cellular senescence, marked increases (5- to 20-fold) were seen in the expression levels of cyclin D2 mRNA and protein. Indirect immunofluorescence studies showed that cyclin D2 protein localized to the nucleus in G(0), suggesting a nuclear function for cyclin D2 in quiescent cells. Cyclin D2 was also found to be associated with the cyclin-dependent kinases CDK2 and CDK4 but not CDK6 during growth arrest. Cyclin D2-CDK2 complexes increased in amounts but were inactive as histone H1 kinases in quiescent cells. Transient transfection and needle microinjection of cyclin D2 expression constructs demonstrated that overexpression of cyclin D2 protein efficiently inhibited cell cycle progression and DNA synthesis. These data suggest that in addition to a role in promoting cell cycle progression through phosphorylation of retinoblastoma family proteins in some cell systems, cyclin D2 may contribute to the induction and/or maintenance of a nonproliferative state, possibly through sequestration of the CDK2 catalytic subunit.