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Science 16 June 2000:
Vol. 288. no. 5473, pp. 2045 - 2047
DOI: 10.1126/science.288.5473.2045
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Reports

Proliferation, But Not Growth, Blocked by Conditional Deletion of 40S Ribosomal Protein S6

Sinisa Volarevic, 1 Mary J. Stewart, 1* Birgit Ledermann, 2 Frederic Zilberman, 1 Luigi Terracciano, 3 Eugenio Montini, 4 Markus Grompe, 4 Sara C. Kozma, 1 George Thomas 1dagger

Because ribosome biogenesis plays an essential role in cell proliferation, control mechanisms may have evolved to recognize lesions in this critical anabolic process. To test this possibility, we conditionally deleted the gene encoding 40S ribosomal protein S6 in the liver of adult mice. Unexpectedly, livers from fasted animals deficient in S6 grew in response to nutrients even though biogenesis of 40S ribosomes was abolished. However, liver cells failed to proliferate or induce cyclin E expression after partial hepatectomy, despite formation of active cyclin D-CDK4 complexes. These results imply that abrogation of 40S ribosome biogenesis may induce a checkpoint control that prevents cell cycle progression.

1 Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058, Basel, Switzerland.
2 University of Zurich, Institute of Laboratory Animal Science, Zurich, Switzerland.
3 University of Basel, Institute of Pathology, Basel, Switzerland.
4 Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland OR 97201, USA.
*   Present address: Department of Zoology, North Dakota State University, Fargo, ND 58105, USA.

dagger    To whom correspondence should be addressed. E-mail: gthomas{at}fmi.ch

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