Mouse development and cell proliferation in the absence of D-cyclins.
Document Type
Article
Publication Date
2004
Keywords
Blotting-Western, CDC2-CDC28-Kinases, Cell-Cycle, Cell-Division, Cell-Transformation-Neoplastic, Cyclin-A, Cyclin-D1, Cyclin-E, Cyclins, Embryo, Fibroblasts, Flow-Cytometry, Gene-Expression-Regulation-Developmental, Hematopoietic-Stem-Cells, Methylcellulose, Mice, Mice-Transgenic, Models-Biological, Phenotype, Protein-Binding, Protein-p16, Research-Support-Non-U, S, -Gov't, Research-Support-U, S, -Gov't-P, H, S, Stem-Cells, Time-Factors
First Page
477
Last Page
491
JAX Source
Cell 2004 Aug; 118(4):477-91.
Abstract
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.
Recommended Citation
Kozar K,
Ciemerych MA,
Rebel VI,
Shigematsu H,
Zagozdzon A,
Sicinska E,
Geng Y,
Yu Q,
Bhattacharya S,
Bronson RT,
Akashi K,
Sicinski P.
Mouse development and cell proliferation in the absence of D-cyclins. Cell 2004 Aug; 118(4):477-91.