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Our study identified the cross\u2010resistance of the cisplatin\u2010selected cells to tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1). Since knock\u2010down of the DDB2 level rendered cells (HR18) sensitive to the treatment, the cell sensitivity to TNF\u2010\u03b1 appears inversely proportional to the cellular level of DDB2. Treatment of HeLa cells with TNF\u2010\u03b1 transiently induced activation of p38MAPK signal, but this induction was significantly reduced in the resistant cells. Overexpression of DDB2 attenuated the activation of p38 in cells. TNF\u2010\u03b1\u2010induced apoptotic signals, represented by caspase\u20108 and downstream substrate cleavage, were reduced in resistant cells compared to their sensitive counterparts. Inhibition of p38 signal by SB202190 clearly attenuated TNF\u2010\u03b1\u2010induced apoptotic signals. Moreover, overexpression of DDB2 in HR18 cells also attenuated TNF\u2010\u03b1 induced caspase activation. These results suggest that p38MAPK activation may be a key upstream signal of TNF\u2010\u03b1\u2010induced apoptosis and that attenuation of p38 signal by DDB2 overexpression may be responsible for acquired TNF\u2010\u03b1 resistance. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20892","type":"journal-article","created":{"date-parts":[[2005,2,7]],"date-time":"2005-02-07T16:18:17Z","timestamp":1107793097000},"page":"383-387","source":"Crossref","is-referenced-by-count":1,"title":["Potential attenuation of p38 signaling by DDB2 as a factor in acquired TNF resistance"],"prefix":"10.1002","volume":"115","author":[{"given":"Chun\u2010Ling","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuck C.\u2010K.","family":"Chao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,4,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1568-7864(02)00052-6"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1568-7864(03)00113-7"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80252-X"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)02250-0"},{"key":"e_1_2_6_6_2","first-page":"723","article-title":"Overexpression of damaged\u2010DNA\u2010binding protein 2 (DDB2) potentiates UV resistance in hamster V79 cells","volume":"25","author":"Sun NK","year":"2002","journal-title":"Chang Gung Med J"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00166-7"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00237-9"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(01)00262-5"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.3.1741"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(97)00042-9"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00542.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2003.10.009"},{"key":"e_1_2_6_14_2","first-page":"601","article-title":"Enhanced host cell reactivation of damaged plasmid DNA in HeLa cells resistant to cis\u2010diamminedichloroplatinum(II)","volume":"51","author":"Chao CC","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02817-4"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.5.2509"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711420112"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0302-221"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.4.657"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.4.2075"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3420249"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.22932"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.7.5124"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.50.33533"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.7.4935"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303229200"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.32.22532"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.20892","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.20892","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T15:23:54Z","timestamp":1697469834000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.20892"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4,7]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,6,20]]}},"alternative-id":["10.1002\/ijc.20892"],"URL":"https:\/\/doi.org\/10.1002\/ijc.20892","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4,7]]}}}