| Autor: |
Liberal V; Department of Molecular Biology, MB-7, The Scripps Research Institute, La Jolla, CA., De Miguel MP, Henze M, Nistal M, Reed SI |
| Jazyk: |
angličtina |
| Zdroj: |
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2010 Oct 15; Vol. 9 (20), pp. 4222-7. Date of Electronic Publication: 2010 Oct 04. |
| DOI: |
10.4161/cc.9.20.13544 |
| Abstrakt: |
Cyclin E is a key component of the cell cycle regulatory machinery, contributing to the activation of Cdk2 and the control of cell cycle progression at several stages. Cyclin E expression is tightly regulated, by periodic transcription and ubiquitin-mediated degradation. Overexpression of cyclin E has been associated with tumor development and poor prognosis in several tumor types, including germ cell tumors and both cyclin E and its partner Cdk2 are required for normal spermatogenesis. Here we have generated and characterized transgenic mice overexpressing a cyclin E mutant protein, resistant to ubiquitin-mediated proteolysis, in testicular germ cells, under the control of the human EF-1alpha promoter. The transgenic mice develop normally and live a normal life span, with no signs of testicular tumor development. The transgenic mice display however reduced fertility and testicular atrophy, due to reduced spermatogonial proliferation as a consequence of deregulated cyclin E levels. Overall our results show that deregulation of cyclin E expression contribute to infertility, due to inability of the spermatogonial cells to start the mitotic cycles prior to entering meiosis. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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