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Molecular and Cellular Biology, July 2001, p. 4246-4255, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4246-4255.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Evidence of p53-Dependent Cross-Talk between Ribosome Biogenesis and the Cell Cycle: Effects of Nucleolar Protein Bop1 on G1/S Transition

Dimitri G. Pestov, Zaklina Strezoska, and Lester F. Lau*

Department of Molecular Genetics, University of Illinois at Chicago College of Medicine, Chicago, Illinois 60607-7170

Received 12 February 2001/Returned for modification 22 March 2001/Accepted 2 April 2001

Bop1 is a novel nucleolar protein involved in rRNA processing and ribosome assembly. We have previously shown that expression of Bop1Delta , an amino-terminally truncated Bop1 that acts as a dominant negative mutant in mouse cells, results in inhibition of 28S and 5.8S rRNA formation and deficiency of newly synthesized 60S ribosomal subunits (Z. Strezoska, D. G. Pestov, and L. F. Lau, Mol. Cell. Biol. 20:5516-5528, 2000). Perturbation of Bop1 activities by Bop1Delta also induces a powerful yet reversible cell cycle arrest in 3T3 fibroblasts. In the present study, we show that asynchronously growing cells are arrested by Bop1Delta in a highly concerted fashion in the G1 phase. Kinase activities of the G1-specific Cdk2 and Cdk4 complexes were downregulated in cells expressing Bop1Delta , whereas levels of the Cdk inhibitors p21 and p27 were concomitantly increased. The cells also displayed lack of hyperphosphorylation of retinoblastoma protein (pRb) and decreased expression of cyclin A, indicating their inability to progress through the restriction point. Inactivation of functional p53 abrogated this Bop1Delta -induced cell cycle arrest but did not restore normal rRNA processing. These findings show that deficiencies in ribosome synthesis can be uncoupled from cell cycle arrest and reveal a new role for the p53 pathway as a mediator of the signaling link between ribosome biogenesis and the cell cycle. We propose that aberrant rRNA processing and/or ribosome biogenesis may cause "nucleolar stress," leading to cell cycle arrest in a p53-dependent manner.

* Corresponding author. Mailing address: Department of Molecular Genetics, University of Illinois at Chicago College of Medicine, 900 S. Ashland Avenue, Chicago, IL 60607-7170. Phone: (312) 996-6978. Fax: (312) 996-7034. E-mail: lflau{at}uic.edu.

Molecular and Cellular Biology, July 2001, p. 4246-4255, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4246-4255.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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