Cyclin D1 promotes mitogen-independent cell cycle progression in hepatocytes.
Cyclin D1 promotes mitogen-independent cell cycle progression in hepatocytes.
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发表时间：
1999-06
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通讯作者：
J. Albrecht;L. Hansen
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作者：
J. Albrecht;L. Hansen
细胞周期蛋白D1被广泛认为是通过细胞周期的G1期调节进展，并且先前的研究表明，这种蛋白质在培养和体内肝细胞增殖期间被诱导。在这项研究中，细胞周期蛋白D1在原代大鼠肝细胞的细胞周期中的作用进行了进一步研究。表皮生长因子刺激后，细胞周期蛋白D1在对应于有丝分裂原限制点的时间点上调，这与增强的细胞周期蛋白D1相关激酶活性有关。为了测试细胞周期蛋白D1的表达是否足以通过G1-S转换促进不依赖于有丝分裂原的进展，我们构建了过表达人细胞周期蛋白D1的复制缺陷型腺病毒。转染细胞周期蛋白D1载体，而不是一个控制载体导致肝细胞DNA合成的生长因子的情况下，这是类似于有丝分裂原处理的细胞中看到的。此外，细胞周期蛋白D1转染导致下游生化事件的激活，包括细胞周期蛋白A和增殖细胞核抗原的表达和细胞周期蛋白E和细胞周期蛋白A相关激酶的激活。这些结果表明，细胞周期蛋白D1的表达足以促进肝细胞通过G1限制点的进展。
Cyclin D1 is widely believed to regulate progression through G1 phase of the cell cycle, and previous studies have shown that this protein is induced during hepatocyte proliferation in culture and in vivo. In this study, the role of cyclin D1 in the cell cycle of primary rat hepatocytes was further examined. Following epidermal growth factor stimulation, cyclin D1 was upregulated at time points corresponding to the mitogen restriction point, and this was associated with enhanced cyclin D1-associated kinase activity. To test whether cyclin D1 expression was sufficient to promote mitogen-independent progression through the G1-S transition, we constructed a replication-defective adenovirus that overexpressed human cyclin D1. Transfection with the cyclin D1 vector but not a control vector resulted in hepatocyte DNA synthesis in the absence of growth factor that was similar to that seen in mitogen-treated cells. Furthermore, cyclin D1 transfection led to activation of downstream biochemical events, including cyclin A and proliferating cell nuclear antigen expression and cyclin E- and cyclin A-associated kinase activation. These results suggest that cyclin D1 expression is sufficient to promote progression of hepatocytes through the G1 restriction point.