N.-H. Zschemisch and C. Liedtke contributed equally to the study.
Liver Biology and Pathobiology
Expression of a cyclin E1 isoform in mice is correlated with the quiescent cell cycle status of hepatocytes in vivo†
Article first published online: 23 JUN 2006
Copyright © 2006 American Association for the Study of Liver Diseases
Volume 44, Issue 1, pages 164–173, July 2006
How to Cite
Zschemisch, N.-H., Liedtke, C., Dierssen, U., Nevzorova, Y. A., Wüstefeld, T., Borlak, J., Manns, M. P. and Trautwein, C. (2006), Expression of a cyclin E1 isoform in mice is correlated with the quiescent cell cycle status of hepatocytes in vivo. Hepatology, 44: 164–173. doi: 10.1002/hep.21224
Potential conflict of interest: Nothing to report.
- Issue published online: 23 JUN 2006
- Article first published online: 23 JUN 2006
- Manuscript Accepted: 9 APR 2006
- Manuscript Received: 18 JUL 2005
- Deutsche Forschungsgemeinschaft. Grant Number: Li1045/2-1
Cyclin E1 controls G1/S phase transition of the eukaryotic cell cycle. We report the impact of alternative spliced cyclin E1 isoforms on cell cycle regulation in hepatocytes. We show that expression of new cyclin E1 mRNA variants IN3, Δ4, and Δ5 is associated with retarded proliferation in murine hepatocellular carcinoma. Additionally, we demonstrate that a new cyclin E1 isoform Δ3/8 lacking the central part of wild-type mRNA is expressed predominantly in nonproliferating murine hepatocytes. Following partial hepatectomy, Δ3/8 is downregulated when hepatocytes enter the cell cycle from quiescence. The Δ3/8 protein does not exhibit any cyclin box motif but binds cyclin-dependent kinase 2 without stimulating kinase activity. We demonstrate that Δ3/8 lacks any nuclear localization signal and is exclusively located in the cytoplasm. Overexpression of Δ3/8 in cultured cells leads to a delayed G0-G1 transition, indicating that this splice variant helps to maintain a quiescent state of hepatocytes. In conclusion, we identified an isoform of cyclin E1 involved in G0 maintenance and suggest an additional mechanism for cell cycle control. (HEPATOLOGY 2006;44:164–173.)