| First Author | Kozar K | Year | 2004 |
| Journal | Cell | Volume | 118 |
| Issue | 4 | Pages | 477-91 |
| PubMed ID | 15315760 | Mgi Jnum | J:92563 |
| Mgi Id | MGI:3053503 | Doi | 10.1016/j.cell.2004.07.025 |
| Citation | Kozar K, et al. (2004) Mouse development and cell proliferation in the absence of D-cyclins. Cell 118(4):477-91 |
| abstractText | D-type cyclins (cyclins D1, D2, and D3) are regarded as essential links between cell environment and the core cell cycle machinery. We tested the requirement for D-cyclins in mouse development and in proliferation by generating mice lacking all D-cyclins. We found that these cyclin D1(-/-)D2(-/-)D3(-/-) mice develop until mid/late gestation and die due to heart abnormalities combined with a severe anemia. Our analyses revealed that the D-cyclins are critically required for the expansion of hematopoietic stem cells. In contrast, cyclin D-deficient fibroblasts proliferate nearly normally but show increased requirement for mitogenic stimulation in cell cycle re-entry. We found that the proliferation of cyclin D1(-/-)D2(-/-)D3(-/-) cells is resistant to the inhibition by p16(INK4a), but it critically depends on CDK2. Lastly, we found that cells lacking D-cyclins display reduced susceptibility to the oncogenic transformation. Our results reveal the presence of alternative mechanisms that allow cell cycle progression in a cyclin D-independent fashion. |
