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

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).

[1]  T. Sugano,et al.  U.v.-induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes independent of the cell cycle. , 1994, Oncogene.

[2]  G. Hannon,et al.  The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA , 1994, Nature.

[3]  Xin Lu,et al.  Differential induction of transcriptionally active p53 following UV or lonizing radiation: Defects in chromosome instability syndromes? , 1993, Cell.

[4]  P. Petronini,et al.  Different HSP70 expression and cell survival during adaptive responses of 3T3 and transformed 3T3 cells to osmotic stress. , 1993, British Journal of Cancer.

[5]  M. Fritsche,et al.  Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents. , 1993, Oncogene.

[6]  D. Lane,et al.  p53, guardian of the genome , 1992, Nature.

[7]  B. Vogelstein,et al.  Participation of p53 protein in the cellular response to DNA damage. , 1991, Cancer research.

[8]  A. Levine,et al.  The p53 tumour suppressor gene , 1991, Nature.

[9]  R. Tyrrell,et al.  Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells. , 1991, Cancer research.

[10]  B. Vogelstein.  A deadly inheritance , 1990, Nature.

[11]  B. Vogelstein,et al.  p53 functions as a cell cycle control protein in osteosarcomas , 1990, Molecular and cellular biology.

[12]  E. Appella,et al.  Wild type human p53 is antiproliferative in SV40-transformed hamster cells. , 1990, Oncogene.

[13]  S. Lindquist.  The heat-shock response. , 1986, Annual review of biochemistry.

[14]  W. Maltzman,et al.  UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells , 1984, Molecular and cellular biology.

[15]  Gloria C. Li.  Induction of thermotolerance and enhanced heat shock protein synthesis in chinese hamster fibroblasts by sodium arsenite and by ethanol , 1983, Journal of cellular physiology.

[16]  M. Mathews,et al.  Molecular and cellular effects of heat-shock and related treatments of mammalian tissue-culture cells. , 1982, Cold Spring Harbor symposia on quantitative biology.

[17]  A. Levine,et al.  Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells , 1981, Molecular and cellular biology.