Cell cycle regulation in H2O2-induced premature senescence of human diploid fibroblasts and regulatory control exerted by the papilloma virus E6 and E7 proteins

C. Frippiat, Q. M. Chen, J. Remacle, O. Toussaint

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Many biomarkers of replicative senescence appear in stress-induced premature senescence (SIPS) of human diploid fibroblasts (HDFs). The mRNA level of key cell cycle regulators was studied in H2O2-induced premature senescence of HDFs expressing or not the papillomavirus E6 and E7 proteins, which enhanced, respectively, the proteolysis of p53 and Rb. The CdKI's p21(waf-1) and p16(Ink-4a) were found overexpressed in H2O2-induced premature senescence, while p19(Ink-4d)and p27(Kip-1) were repressed. The results obtained in E6 HDFs suggest that p21(waf-1) and p16(Ink-4a) overexpressions are p53-independent, while p27(Kip-1) and p19(Ink-4d) down-regulations are p53-dependent. E6 regulated Rb, p130, p53 and p16(Ink-4a) mRNA level in non-stressing conditions, and regulated p130, p107, p53, p19(Ink-4d), p27(Kip-1) mRNA level in SIPS. SIPS modified the E6-mediated regulatory control on p107, p16(Ink-4a), p19(Ink-4d) and p27(Kip-1) mRNA level, when compared to normal conditions. E7 regulated the mRNA level of all the genes studied, in all conditions, suggesting that the Rb family or other E7-interacting proteins might modify the expression of these genes. SIPS modified strongly the E7-mediated regulatory control on p107, p16(Ink-4a), p19(Ink-4d), p27(Kip-1), p21(Waf-1) and Rb mRNA level, when compared to normal conditions. Further work is ongoing to test whether this E7-mediated regulatory control takes place through interactions with Rb or other E7-interacting proteins. (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)733-745
Number of pages13
JournalExperimental Gerontology
Volume35
Issue number6-7
DOIs
StatePublished - Nov 7 2000

Keywords

  • Aging
  • CdKI
  • HO
  • Stress-induced premature senescence
  • p53
  • pRb

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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