Cyclin D1 and p21/waf1 are both involved in p53 growth suppression

Giannino Del Sal, Maureen Murphy, Elisabetta M. Ruaro, Dean Lazarevic, Arnold J. Levine, Claudio Schneider

Research output: Contribution to journalArticlepeer-review

Abstract

Overexpression of the wild type p53 gene in normal and transformed cells induces G1 arrest of cellular proliferation. In cell lines carrying the valine 135 temperature-sensitive p53 mutant gene, restoration of wild type p53 protein conformation at the permissive temperature causes an increase in the levels of cyclin D1, as well as the cyclin/cdk inhibitor p21/waf1. Accumulation of cyclin D1 is the result both of (post)transcriptional and post-translational regulatory mechanisms. Ablation of cyclin D1 induction by antisense cDNA microinjection significantly delays the onset of growth arrest, indicating that increased cyclin D1 levels likely contribute to wild type p53 G1 arrest. Whereas antisense ablation of either cyclin D1 or p21/ waf1 can delay the onset of p53-induced growth arrest, ablation of neither is able to overcome a pre-existing p53-induced C1 block. In summary, the accumulated evidence indicate that induction of both cyclin D1 and p21/waf1 are involved in establishing the p53-mediated growth arrest in murine cell lines expressing temperature sensitive p53 protein.

Original languageEnglish
Pages (from-to)177-185
Number of pages9
JournalOncogene
Volume12
Issue number1
Publication statusPublished - 1996

Keywords

  • Cell cycle G1 arrest
  • Cyclin
  • D1
  • p21/waf1
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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