Cell Growth & Differentiation, Vol 5, Issue 1 99-108, Copyright © 1994 by American Association of Cancer Research

ARTICLES

Posttranscriptional regulation of cyclin B messenger RNA expression in the regenerating rat liver

JH Trembley, BT Kren and CJ Steer
Department of Medicine, University of Minnesota, Minneapolis 55455.

The growing family of cyclin genes and their products have been identified as important regulatory participants in the eukaryotic cell cycle. Cyclin proteins are currently postulated to act at the G1 restriction point, entry and exit of S phase, and the G2-M transition. We have cloned a rat cyclin B complementary DNA (cDNA) and have investigated cyclin B mRNA expression and regulation in the regenerating rat liver following 70% partial hepatectomy (PH). Sequence analysis of the rat cyclin cDNA revealed greater than 82% identity to type B1 human and murine cyclin genes. The rat cyclin cDNA was used to probe Northern blots of polyadenylated enriched RNA from regenerating rat liver from 0 through 96 h post-PH. Two species of rat cyclin B transcript were detected which mapped at 1.6 and 2.4 kilobases in length. Steady-state transcript levels began to appear around 24 h post-PH, which coincides with peak DNA synthesis. However, expression of the cyclin B transcripts peaked at 48 h and was 20-fold greater than at 24 h post-PH. Smaller peaks of expression occurred at 30 and 72 h. Run-off transcription assays using nuclei isolated at various times post-PH indicated no change in transcriptional rate during the period of regeneration. In vivo mRNA half-life determinations were performed at 24, 40, and 48 h post-PH. The half-lives of both transcript species were almost identical and were determined to be greater than 12 h at 24 h post-PH, and 2.4 h at 40 and 48 h post-PH. Protein inhibition with cycloheximide increased the signal intensity of both transcripts between 48 and 54 h post-PH but had no detectable effect on 0 h transcript expression. Steady-state levels of thymidine kinase mRNA showed a similar pattern of expression by Northern analysis through 96 h post-PH as cyclin B. The present study indicates that the appearance of cyclin B mRNA in the regenerating rat liver is coincident with peak DNA synthesis, although its own peak expression is significantly delayed. Steady-state transcript levels appear to be regulated primarily by posttranscriptional events of which changes in mRNA stability may be an important determinant. We propose that the involvement of cyclin B in the cell cycle machinery is controlled at several different levels of gene expression.

This article has been cited by other articles:

				N. C. Joyce, D. L. Harris, J. C. Mc Alister, R. R. Ali, and D. F. P. Larkin Effect of Overexpressing the Transcription Factor E2F2 on Cell Cycle Progression in Rabbit Corneal Endothelial Cells Invest. Ophthalmol. Vis. Sci., May 1, 2004; 45(5): 1340 - 1348. [Abstract] [Full Text] [PDF]

				E. Matthew, L. Kutcher, and J. Dedman Protection of lungs from hyperoxic injury: gene expression analysis of cyclosporin A therapy Physiol Genomics, July 7, 2003; 14(2): 129 - 138. [Abstract] [Full Text] [PDF]

				J. I. Leu, M. A. S. Crissey, L. E. Craig, and R. Taub Impaired Hepatocyte DNA Synthetic Response Posthepatectomy in Insulin-Like Growth Factor Binding Protein 1-Deficient Mice with Defects in C/EBP{beta} and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Regulation Mol. Cell. Biol., February 15, 2003; 23(4): 1251 - 1259. [Abstract] [Full Text] [PDF]

				S Vee, L Lafanechere, D Fisher, J Wehland, D Job, and A Picard Evidence for a role of the (alpha)-tubulin C terminus in the regulation of cyclin B synthesis in developing oocytes J. Cell Sci., January 3, 2001; 114(5): 887 - 898. [Abstract] [PDF]

				S. R. Jones, B. F. Kimler, W. M. Justice, and V. Rider Transit of Normal Rat Uterine Stromal Cells through G1 Phase of the Cell Cycle Requires Progesterone-Growth Factor Interactions Endocrinology, February 1, 2000; 141(2): 637 - 648. [Abstract] [Full Text] [PDF]

				H. Ye, A. X. Holterman, K. W. Yoo, R. R. Franks, and R. H. Costa Premature Expression of the Winged Helix Transcription Factor HFH-11B in Regenerating Mouse Liver Accelerates Hepatocyte Entry into S Phase Mol. Cell. Biol., December 1, 1999; 19(12): 8570 - 8580. [Abstract] [Full Text] [PDF]

				G. Servillo, M. A. Della Fazia, and P. Sassone-Corsi Transcription factor CREM coordinates the timing of hepatocyte proliferation in the regenerating liver Genes & Dev., December 1, 1998; 12(23): 3639 - 3643. [Abstract] [Full Text]

				C. Knouff, S. Malloy, J. Wilder, M. K. Altenburg, and N. Maeda Doubling Expression of the Low Density Lipoprotein Receptor by Truncation of the 3'-Untranslated Region Sequence Ameliorates Type III Hyperlipoproteinemia in Mice Expressing the Human ApoE2 Isoform J. Biol. Chem., February 2, 2001; 276(6): 3856 - 3862. [Abstract] [Full Text] [PDF]