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.
aklina
Strezoska, andDepartment 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 Bop1
,
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 Bop1
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 Bop1
in a highly concerted fashion in the G1
phase. Kinase activities of the G1-specific Cdk2 and Cdk4
complexes were downregulated in cells expressing Bop1
, 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 Bop1
-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.
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