Cyclin D3 is rate-limiting for the G1/S phase transition in fibroblasts
Cyclin D3 is rate-limiting for the G1/S phase transition in fibroblasts
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DOI：
10.1074/jbc.273.24.14958
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发表时间：
1998-06-12
影响因子：
4.8
通讯作者：
Reed, SI
中科院分区：
文献类型：
--
作者：
Henzinger, T;Reed, SI
d型细胞周期蛋白是在有丝分裂原的诱导下被诱导的，并且被认为通过激活相应的激酶伙伴（细胞周期蛋白依赖激酶）来控制细胞周期的G(1)期的进展。为了研究单个d型细胞周期蛋白的功能，我们构建了允许人类细胞周期蛋白D3 cDNA可控过表达的大鼠成纤维细胞系。cyclin D3过表达导致活跃增殖细胞通过G(1)的速度加快，但对总体群体倍增时间没有影响。在从静止状态重新进入分裂周期的细胞中，cyclin D3导致S期进入更为显著的提前。通过G(0)/G(1)到s的加速进展与髓肿瘤抑制蛋白及其相关蛋白p107和p130的过早磷酸化相关。我们得出结论，细胞周期蛋白D3可以作为限速的G(1)细胞周期蛋白，这种作用部分涉及关键底物的过早磷酸化。
D-type cyclins are induced in response to mitogens and are believed to control progression through the G(1) phase of the cell cycle by activating their corresponding kinase partners (cyclin-dependent kinases). To investigate the function of individual D-type cyclins we have constructed rat fibroblast lines that allow controllable overexpression of a human cyclin D3 cDNA. Overexpression of cyclin D3 led to accelerated passage through G(1) in actively proliferating cells with no effect on the overall population doubling time. In cells re-entering the division cycle from a quiescent state, cyclin D3 caused an even more dramatic advancement of S phase entry. Accelerated progression through G(0)/G(1)-to-S correlated with premature phosphorylation of the pith tumor suppressor protein and its relatives, p107 and p130. We conclude that cyclin D3 can act as a rate-limiting G(1) cyclin and that this effect involves, in part, the premature phosphorylation of critical substrates.