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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1995 May;86(5):415–418. doi: 10.1111/j.1349-7006.1995.tb03072.x

Nuclear Accumulation of p53 in Normal Human Fibroblasts Is Induced by Various Cellular Stresses which Evoke the Heat Shock Response, Independently of the Cell Cycle

Tatsuo Sugano 1, Makoto Nitta 1,2, Hiroyuki Ohmori 1, Masaru Yamaizumi 1,✉
PMCID: PMC5920847  PMID: 7790313

Abstract

Nuclear accumulation of p53 is induced by various DNA damaging agents (the p53 response). Induction of nuclear accumulation of p53 after various cellular stresses, mostly other than DNA damage, including heat shock, was examined in normal human fibroblasts by immunostaining and flow cytometry using a mouse anti‐p53 monoclonal antibody. Immunostaining revealed nuclear accumulation of p53 within 6 h after various stresses [heat shock, osmotic shock, heavy metal (Cd), blockers of the cellular respiratory system (NaN3), amino acid analogues (azetidine and canavanine), an inhibitor of protein synthesis (puromycin), and oxygen free radicals (H2O2)]. Heat shock proved to be one of the most effective inducers among these stresses. FACScan analysis revealed that this induction of p53 occurred regardless of the stage in the cell cycle and that accumulation of cells in G2/M occurred. As all of these stresses are known to induce the heat shock response, the mechanism of p53 induction after stresses and that of heat shock response may share, at least partly, some common signaling pathway(s).

Keywords: p53 response, Heat shock response, Cell cycle, Cellular stress

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REFERENCES

  • 1).Vogelstein , B.A deadly inheritance . Nature , 348 , 681 – 682 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 2).Diller , L. , Kassel , J. , Nelson , C. E. , Gryka , M. A. , Litwac , G. , Gebhardt , M. , Bressac , B. , Ozturk , M. , Baker , S. J. , Vogelstein , B. and Friend , S. H.p53 functions as a cell cycle control protein in osteosarcomas . Mol. Cell. Biol. , 10 , 5772 – 5781 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3).Mercer , W. E. , Amin , M. , Sauve , G. J. , Appella , E. , Ullrich , S. J. and Romano , J. W.Wild type human p53 is antiproliferative in SV40‐transformed hamster cells . Oncogene , 5 , 973 – 980 ( 1990. ). [PubMed] [Google Scholar]
  • 4).Levine , A. J. , Momand , J. and Finlay , C.The p53 tumour suppressor gene . Nature , 351 , 453 – 456 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 5).Oren , M. , Maltzman , W. and Levine , A. J.Post translational regulation of the 54K cellular tumor antigen in normal and transformed cells . Mol. Cell. Biol. , 1 , 101 – 110 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6).Fritsche , M. , Haessler , C. and Brander , G.Induction of nuclear accumulation of the tumor‐suppressor protein p53 by DNA‐damaging agent . Oncogene , 8 , 307 – 318 ( 1993. ). [PubMed] [Google Scholar]
  • 7).Lu , X. and Lane , D. P.Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndrome ? Cell , 75 , 765 – 778 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 8).Yamaizumi , M. and Sugano , T.UV‐induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes independent of the cell cycle . Oncogene , 9 , 2775 – 2784 ( 1994. ). [PubMed] [Google Scholar]
  • 9).Maltzman , W. and Czyzyk , L.UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells . Mol. Cell. Biol. , 4 , 1689 – 1694 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10).Kastan , M. B. , Onyekwere , O. , Sidransky , D. , Vogelstein , B. and Craig , R. W.Participation of p53 protein in the cellular response to DNA damage . Cancer Res. , 51 , 6304 – 6311 ( 1991. ). [PubMed] [Google Scholar]
  • 11).Lane , D. P.p53, guardian of the genome . Nature , 358 , 15 – 16 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 12).Waga , S. , Hannon , G. J. , Beach , D. and Stillman , B.The p21 inhibitor of cyclin‐dependent kinases controls DNA replication by interaction with PCNA . Nature , 369 , 574 – 578 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 13).Petronini , P. G. , Alfieri , R. , De Angelis , E. , Campanini , C. , Borghetti , A. F. and Wheeler , K. P.Different HSP70 expression and cell survival during adaptive responses of 3T3 and transformed 3T3 cells to osmotic stress . Br. J. Cancer , 67 , 493 – 499 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14).Thomas , G. P. , Welch , W. J. , Mathews , M. B. and Feramisco , J. R.Molecular and cellular effects of heat‐shock and related treatments of mammalian tissue‐culture cells . Cold Spring Harbor Symp. Quant. Biol. , 46 , 985 – 996 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 15).Lindquist , S.The heat shock response . Annu. Rev. Biochem. , 55 , 1151 – 1191 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 16).Applegate , L. A. , Luscher , P. and Tyrrell , R. M.Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells . Cancer Res. , 51 , 974 – 978 ( 1991. ). [PubMed] [Google Scholar]
  • 17).Li , G. C.Induction of thermotolerance and enhanced heat shock protein synthesis in Chinese hamster fibroblasts by sodium arsenite . J. Cell. Physiol. , 115 , 116 – 122 ( 1983. ). [DOI] [PubMed] [Google Scholar]

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