Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: Effects of nucleolar protein Bop1 on G1/S transition

D. G. Pestov, Ž Strezoska, L. F. Lau

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259 Scopus citations

Abstract

Bop1 is a novel nucleolar protein involved in rRNA processing and ribosome assembly. We have previously shown that expression of Bop1Δ, 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 Bop1Δ 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 Bop1Δ in a highly concerted fashion in the G1 phase. Kinase activities of the G1-specific Cdk2 and Cdk4 complexes were downregulated in cells expressing Bop1Δ, 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 Bop1Δ-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.

Original languageEnglish (US)
Pages (from-to)4246-4255
Number of pages10
JournalMolecular and Cellular Biology
Volume21
Issue number13
DOIs
StatePublished - 2001

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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