TY - JOUR
T1 - Cyclin A Is Redundant in Fibroblasts but Essential in Hematopoietic and Embryonic Stem Cells
AU - Kalaszczynska, Ilona
AU - Geng, Yan
AU - Iino, Tadafumi
AU - Mizuno, Shin ichi
AU - Choi, Yoon
AU - Kondratiuk, Ilona
AU - Silver, Daniel P.
AU - Wolgemuth, Debra J.
AU - Akashi, Koichi
AU - Sicinski, Piotr
N1 - Funding Information:
We thank members of the Sicinski lab, R. Bronson, E. Sicinska, M.A. Ciemerych-Litwinienko, A. Minamishima, S. Kobayashi, and B. Will for help and advice, B. Clurman for anti-cyclin E1 antibody, and F. Liu for anti-phospho Smad3 antibodies. This work was supported by R01CA132740 and R01CA108950 grants from the National Institutes of Health (to P.S.) and R01 HD34915 (to D.J.W.). P.S. is a Scholar of The Leukemia and Lymphoma Society.
PY - 2009/7/23
Y1 - 2009/7/23
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2009.04.062
DO - 10.1016/j.cell.2009.04.062
M3 - Article
C2 - 19592082
AN - SCOPUS:67650638697
SN - 0092-8674
VL - 138
SP - 352
EP - 365
JO - Cell
JF - Cell
IS - 2
ER -