Cyclin D3: requirement for G1/S transition and high abundance in quiescent tissues suggest a dual role in proliferation and differentiation
Cyclin D3: requirement for G1/S transition and high abundance in quiescent tissues suggest a dual role in proliferation and differentiation
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DOI：
10.1038/sj.onc.1202016
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发表时间：
1998-08-27
期刊：
影响因子：
8
通讯作者：
Bartek, J
中科院分区：
文献类型：
--
作者：
Bartkova, J;Lukas, J;Bartek, J
哺乳动物D型细胞周期蛋白D1、D2和D3激活G1期细胞周期蛋白依赖性激酶CDK 4和CDK 6，从而促进细胞进入S期。为了阐明D-型细胞周期蛋白之间的功能重叠的程度，我们已经研究了几个方面的G1细胞周期蛋白，细胞周期蛋白D3，这个亚家族的最小特征的成员。显微注射细胞周期蛋白D3中和抗体抑制人（IMR-90）和大鼠（R12）二倍体成纤维细胞的G1/S转换，表明类似于细胞周期蛋白D1和D2，细胞周期蛋白D3是必要的及时通过GF进展。与细胞周期蛋白D1和D2相反，细胞周期蛋白D3（i）在一组70种人类培养细胞类型中普遍表达;（ii）在诱导HL-60白血病细胞分化时强烈上调;（iii）在小鼠和人类分化组织中广泛的静止细胞类型中积累至高水平。在胎儿和出生后发育的不同阶段，人类活检和小鼠组织的互补分析显示细胞周期蛋白D3蛋白的谱系依赖性瞬时或长期积累，分别与成熟表型的启动/建立或维持相关。我们的数据支持的概念，个别D-型细胞周期蛋白的生物学作用是不完全多余的，并建议细胞周期蛋白D3在细胞增殖和诱导和/或维持终末分化可能的双重作用。
The mammalian D-type cyclins DI, D2, and D3 activate the cyclin-dependent kinases CDK4 and CDK6 in G1 and thereby promote the cell's commitment to enter S phase. To elucidate the extent of functional overlap among the D-type cyclins, we have examined several aspects of the least characterized member of this subfamily of G1 cyclin proteins, cyclin D3. Microinjection of cyclin D3-neutralizing antibody inhibited G1/S transition in human (IMR-90) and rat (R12) diploid fibroblasts, indicating that analogous to cyclins D1 and D2, cyclin D3 is essential for timely progression through Gf. In contrast to cyclins D1 and D2, cyclin D3 was (i) ubiquitously expressed among a panel of 70 human cultured cell types; (ii) strongly upregulated upon induction of HL-60 leukaemia cells to differentiate; and (iii) accumulated to high levels in a wide range of quiescent cell types in mouse and human differentiated tissues. Complementary analyses of human biopsies and mouse tissues at different stages of foetal and postnatal development revealed lineage-dependent transient or long-term accumulation of the cyclin D3 protein, correlating with initiation/establishment or maintenance of the mature phenotypes, respectively. Our data support the notion that the biological roles of the individual D-type cyclins are not fully redundant, and suggest a possible dual role for cyclin D3 in cell proliferation and induction and/or maintenance of terminal differentiation.