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Expression of a cyclin E1 isoform in mice is correlated with the quiescent cell cycle status of hepatocytes in vivo
Author(s) -
Zschemisch NilsHolger,
Liedtke Christian,
Dierssen Uta,
Nevzorova Yulia A.,
Wüstefeld Torsten,
Borlak Jürgen,
Manns Michael P.,
Trautwein Christian
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21224
Subject(s) - cyclin e1 , cyclin a , cell cycle , biology , cyclin e , microbiology and biotechnology , cyclin b1 , cyclin , cyclin d1 , cyclin d , cyclin a2 , gene isoform , cyclin b , cancer research , cell , cyclin dependent kinase 1 , biochemistry , gene
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. (H EPATOLOGY 2006;44:164–173.)