Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells
Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells
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DOI：
10.1038/sj.onc.1208356
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发表时间：
2005-04-14
期刊：
影响因子：
8
通讯作者：
Müller-Tidow, C
中科院分区：
文献类型：
--
作者：
Ji, P;Agrawal, S;Müller-Tidow, C
细胞周期蛋白A1是另一种对精子发生至关重要的a型细胞周期蛋白，但它也在造血祖细胞和急性髓性白血病中表达。其在体细胞周期进程中的作用尚不完全清楚。在这里，我们分析了细胞周期蛋白A1在转化和非转化细胞中的细胞周期功能。来源于细胞周期蛋白a1缺陷小鼠的小鼠胚胎成纤维细胞增殖能力明显受损。细胞周期蛋白A1（-/-）细胞在G1期和G2/M期积累，S期细胞比例下降。此外，凝集素刺激的细胞周期蛋白A1（-/-）小鼠脾淋巴细胞增殖速度比野生型小鼠慢。在NIH3T3细胞和U937白血病细胞中，通过瞬时转染或逆转录病毒感染强制cyclin A1过表达可增强S期进入。因此，在高cyclin A1表达的ML1白血病细胞中，siRNA介导的cyclin A1沉默显著减缓了S期进入，降低了增殖并抑制了集落形成。综上所述，这些分析表明，细胞周期蛋白A1有助于体细胞G1到S细胞周期的进展。Cyclin A1过表达增强了S期进入，这与致癌功能一致。最后，细胞周期蛋白A1可能是一个治疗靶点，因为它的沉默抑制白血病细胞的生长。
Cyclin A1 is an alternative A-type cyclin that is essential for spermatogenesis, but it is also expressed in hematopoietic progenitor cells and in acute myeloid leukemia. Its functions during cell cycle progression of somatic cells are incompletely understood. Here, we have analysed the cell cycle functions of cyclin A1 in transformed and non-transformed cells. Murine embryonic fibroblasts derived from cyclin A1-deficient mice were significantly impaired in their proliferative capacity. In accordance, cyclin A1(-/-) cells accumulated in G1 and G2/M phase while the percentage of S phase cells decreased. Also, lectin stimulated splenic lymphocytes from cyclin A1(-/-) mice proliferated slower than their wild-type counterparts. Forced cyclin A1 overexpression in NIH3T3 cells and in U937 leukemic cells either by transient transfection or by retroviral infection enhanced S phase entry. Consequently, siRNA mediated silencing of cyclin A1 in highly cyclin A1 expressing ML1 leukemic cells significantly slowed S phase entry, decreased proliferation and inhibited colony formation. Taken together, these analyses demonstrate that cyclin A1 contributes to G1 to S cell cycle progression in somatic cells. Cyclin A1 overexpression enhances S phase entry consistent with an oncogenic function. Finally, cyclin A1 might be a therapeutic target since its silencing inhibited leukemia cell growth.