Cyclin A Is Redundant in Fibroblasts but Essential in Hematopoietic and Embryonic Stem Cells

被引:164
作者
Kalaszczynska, Ilona [1 ,4 ]
Geng, Yan [1 ,4 ]
Iino, Tadafumi [2 ,4 ]
Mizuno, Shin-ichi [2 ,4 ]
Choi, Yoon [1 ,4 ]
Kondratiuk, Ilona [1 ,4 ]
Silver, Daniel P. [3 ,5 ]
Wolgemuth, Debra J. [6 ,7 ]
Akashi, Koichi [2 ,4 ]
Sicinski, Piotr [1 ,4 ]
机构
[1] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA
[2] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA
[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[6] Columbia Univ, Ctr Med, Dept Genet & Dev, New York, NY 10032 USA
[7] Columbia Univ, Ctr Med, Dept Obstet & Gynecol, New York, NY 10032 USA
基金
美国国家卫生研究院;
关键词
DEPENDENT KINASES; C-MYC; EXPRESSION; PROGRESSION; GENE; MICE; MOUSE; PROLIFERATION; ACCUMULATION; PROGENITOR;
D O I
10.1016/j.cell.2009.04.062
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cyclins are regulatory subunits of cyclin-dependent kinases. Cyclin A, the first cyclin ever cloned, is thought to be an essential component of the cell-cycle engine. Mammalian cells encode two A-type cyclins, testis-specific cyclin A1 and ubiquitously expressed cyclin A2. Here, we tested the requirement for cyclin A function using conditional knockout mice lacking both A-type cyclins. We found that acute ablation of cyclin A in fibroblasts did not affect cell proliferation, but led to prolonged expression of another cyclin, cyclin E, across the cell cycle. However, combined ablation of all A- and E-type cyclins extinguished cell division. In contrast, cyclin A function was essential for cell-cycle progression of hematopoietic and embryonic stem cells. Expression of cyclin A is particularly high in these compartments, which might render stem cells dependent on cyclin A, whereas in fibroblasts cyclins A and E play redundant roles in cell proliferation.
引用
收藏
页码:352 / 365
页数:14
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