Cyclin E ablation in the mouse.
E type cyclins (E1 and E2) are believed to drive cell entry into the S phase. It is widely assumed that the two E type cyclins are critically required for proliferation of all cell types. Here, we demonstrate that E type cyclins are largely dispensable for mouse development. However, endoreplication of trophoblast giant cells and megakaryocytes is severely impaired in the absence of cyclin E. Cyclin E-deficient cells proliferate actively under conditions of continuous cell cycling but are unable to reenter the cell cycle from the quiescent G(0) state. Molecular analyses revealed that cells lacking cyclin E fail to normally incorporate MCM proteins into DNA replication origins during G(0)-->S progression. We also found that cyclin E-deficient cells are relatively resistant to oncogenic transformation. These findings define a molecular function for E type cyclins in cell cycle reentry and reveal a differential requirement for cyclin E in normal versus oncogenic proliferation.
Geng
Yan
Y
Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Yu
Qunyan
Q
Sicinska
Ewa
E
Das
Manjusri
M
Schneider
Jürgen E
JE
Bhattacharya
Shoumo
S
Rideout
William M
WM
Bronson
Roderick T
RT
Gardner
Humphrey
H
Sicinski
Piotr
P
D000818:Animals; D018376:Cardiovascular Abnormalities; D002453:Cell Cycle / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism*; D004261:DNA Replication; D004622:Embryo, Mammalian / Q000502:physiology*; D005260:Female; D018390:Gene Targeting; D008297:Male; D008533:Megakaryocytes / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D013091:Spermatogenesis / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D019927:Cyclin E