{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:05:37Z","timestamp":1767902737364,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,1,11]],"date-time":"2002-01-11T00:00:00Z","timestamp":1010707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2002,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although p53 responses after DNA damage have been investigated extensively, p53 responses after heat shock, which exerts cytotoxic action by mechanisms other than direct induction of DNA damage, are less well characterized. We investigated, therefore, the effect of hyperthermic exposures on the levels and DNA\u2010binding activity of p53. Experiments were carried out with U2OS and ML\u20101 cells, known to express wild\u2010type p53 protein. Although heating at 41\u00b0C for up to 6 h had only a small effect on p53 levels or DNA binding activity, exposure to temperatures between 42.5 and 45.5\u00b0C caused an immediate decrease in protein levels that was associated with a reduction in DNA binding activity. This observation is compatible with a high lability of p53 to heat shock, or heat sensitivity of the pathway regulating p53 levels in non\u2010stressed cells. When cells were heated to 42.5\u00b0C and returned to normal temperatures, a strong p53 response associated with an increase in protein levels and DNA binding activity was observed, suggesting the production of p53\u2010inducing cellular damage. At higher temperatures, however, this response was compromised in an exposure\u2013time\u2010dependent manner. The increase in DNA binding activity was more heat sensitive than the increase in p53 levels and was inhibited at lower temperatures and shorter exposure times. Thus, the pathway of p53 activation is itself heat sensitive and compromised at high levels of exposure. Compared to p53 activation after exposure to ionizing radiation, heat\u2010induced activation is rapid and short lived. When cells were exposed to combined heat and radiation, the response observed approximated that of cells exposed to heat alone. Wortmannin at 10 \u03bcM inhibited p53 activation for up to 2 h after heat shock suggesting the involvement of wortmannin\u2010sensitive kinases, such as DNA\u2010PK and ATM. Heat shock causes phosphorylation of p53 at Serine\u201015, but there is no correlation between phosphorylation at this site and activation of the protein. The results in aggregate indicate p53 activation in the absence of DNA damage by a heat\u2010sensitive mechanism operating with faster kinetics than radiation\u2010induced p53 activation. The former response may induce pathways preventing other stimuli from activating p53, as heat\u2010induced activation of p53 is dominant over activation of p53 by DNA damage in combined\u2010treatment experiments. These observations suggest means for abrogating p53 induction after DNA damage with the purpose of potentiating response and enhancing cell killing. J. Cell. Physiol. 190: 365\u2013374, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.10069","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T04:51:41Z","timestamp":1030251101000},"page":"365-374","source":"Crossref","is-referenced-by-count":27,"title":["Effects of hyperthermia on p53 protein expression and activity"],"prefix":"10.1002","volume":"190","author":[{"given":"Jun","family":"Guan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Stavridi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis B.","family":"Leeper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Iliakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,1,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.914401"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1674"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8379"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1677"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.3.278"},{"key":"e_1_2_6_7_1","first-page":"589","volume-title":"Radiation biology in cancer research","author":"Dewey WC","year":"1980"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553009214550851"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.11.5772"},{"key":"e_1_2_6_10_1","first-page":"595","article-title":"Specific interaction between a subset of the p53 protein family and heat shock proteins hsp72\/hsc73 in a human osteosarcoma cell line","volume":"3","author":"Ehrhart JC","year":"1988","journal-title":"Oncogene"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.31.19471"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.41.25468"},{"key":"e_1_2_6_13_1","first-page":"307","article-title":"Induction of nuclear accumulation of the tumor\u2010suppressor protein p53 by DNA\u2010damaging agents","volume":"8","author":"Fritsche M","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.19.2973"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.9.6264"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/379088a0"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-4193-2"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05434.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1995.48"},{"key":"e_1_2_6_20_1","first-page":"203","article-title":"High levels of p53 protein in UV\u2010irradiated normal human skin","volume":"8","author":"Hall PA","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.7.3917"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.1507"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.41.26009"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/095530099140717"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00016a002"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.2307\/3576063"},{"key":"e_1_2_6_27_1","first-page":"6304","article-title":"Participation of p53 protein in the cellular response to DNA damage","volume":"51","author":"Kastan MB","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_6_28_1","first-page":"2580","article-title":"Apoptosis as a predictor of taxol\u2010induced radiosensitization in human tumor cell lines","volume":"5","author":"Kurdoglu B","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)91174-O"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90496-D"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(94)90407-3"},{"key":"e_1_2_6_32_1","first-page":"741","article-title":"Suppression of heat\u2010induced p53 accumulation and activation by CDDP or X\u2010rays in human glioblastoma cells","volume":"13","author":"Matsumoto H","year":"1998","journal-title":"Int J Oncol"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.4.2828"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/095530097143851"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(93)90262-8"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.3109\/02656739509022498"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.24.14510"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/095530000138385"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.1.2.101"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.3.1449"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/320182a0"},{"key":"e_1_2_6_42_1","first-page":"246","article-title":"The phosphatidylinositol 3\u2010kinase inhibitor Wortmannin sensitizes murine fibroblasts and human tumor cells to radiation and blocks induction of p53 following DNA damage","volume":"56","author":"Price BD","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1379\/1466-1268(1998)003<0245:NMAATF>2.3.CO;2"},{"key":"e_1_2_6_44_1","first-page":"4375","article-title":"Inhibition of phosphoinositide 3\u2010kinase related kinases by the radiosensitizing agent wortmannin","volume":"58","author":"Sarkaria JN","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150171114"},{"key":"e_1_2_6_46_1","first-page":"285","article-title":"Mild hyperthermia\u2010induced apoptosis is dependent on p53 in human lymphoid cells","volume":"104","author":"Seo Y\u2010R","year":"1999","journal-title":"Res Comm Molec Path Pharm"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.25.15084"},{"key":"e_1_2_6_48_1","first-page":"289","article-title":"The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage\u2010inducible sites [published erratum appears in Genes Dev 2000 Mar 15;14(6):750]","volume":"14","author":"Shieh SY","year":"2000","journal-title":"Genes Dev"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.8.916"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1995.tb03072.x"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19970717)72:2<307::AID-IJC18>3.0.CO;2-C"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/348681a0"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellbi.2006.11.012"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.45.29586"},{"key":"e_1_2_6_55_1","first-page":"8554","article-title":"Replication protein A2 phosphorylation after DNA damage by the coordinated action of ataxia telangiectasia\u2010mutated and DNA\u2010dependent protein kinase","volume":"61","author":"Wang H","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.14.2188"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.7.4242"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.10069","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.10069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T08:09:53Z","timestamp":1700294993000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.10069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1,24]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2002,3]]}},"alternative-id":["10.1002\/jcp.10069"],"URL":"https:\/\/doi.org\/10.1002\/jcp.10069","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,1,24]]}}}