Mouse development and cell proliferation in the absence of D-cyclins

Katarzyna Kozar, Maria A. Ciemerych, Vivienne I. Rebel, Hirokazu Shigematsu, Agnieszka Zagozdzon, Ewa Sicinska, Yan Geng, Qunyan Yu, Shoumo Bhattacharya, Roderick T. Bronson, Koichi Akashi, Piotr Sicinski

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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 p16INK4a, 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.

Original languageEnglish
Pages (from-to)477-491
Number of pages15
JournalCell
Volume118
Issue number4
DOIs
Publication statusPublished - Aug 20 2004
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kozar, K., Ciemerych, M. A., Rebel, V. I., Shigematsu, H., Zagozdzon, A., Sicinska, E., ... Sicinski, P. (2004). Mouse development and cell proliferation in the absence of D-cyclins. Cell, 118(4), 477-491. https://doi.org/10.1016/j.cell.2004.07.025