Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic stem cells.
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.
Kalaszczynska
Ilona
I
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Geng
Yan
Y
Iino
Tadafumi
T
Mizuno
Shin-ichi
S
Choi
Yoon
Y
Kondratiuk
Ilona
I
Silver
Daniel P
DP
Wolgemuth
Debra J
DJ
Akashi
Koichi
K
Sicinski
Piotr
P
D000818:Animals; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism*; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
D019925:Cyclin A; D019927:Cyclin E