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We show here that the TNF\u03b1 gene, a pleiotropic N\u03baBS inducer, is a direct target of heat shock factor 1 (HSF1). Human HSF1 drives this process by assembling a multiprotein activation complex at a heat shock element (HSE) located at the 3\u2032\u2010UTR of the TNF\u2010\u03b1 gene (HSE5). HSF1 associated with the HSE5 at the TNF\u2010\u03b1 3\u2032\u2010UTR communicates with the promoter through chromatin looping by recruiting lymphoid enhancer\u2013binding factor 1 at an adjacent Wnt\u2010responsive element through its transactivation domain. TNF\u2010\u03b1 thus produced guides the activation of N\u03baBS by acting through TNF\u2010\u03b1 receptor 1 (TNFR1). Notably, cells with TNFR1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    background or masked HSE5 through Clustered Regularly Interspaced Short Palindromic Repeats\/dead CRISPR\u2010associated protein 9 were defective in N\u03baBS and exhibited marked alteration in cellular biology, which includes loss of ability of cancer cells to migrate, to clear the protein aggregates, and associated toxicity upon heat shock. For the first time, our results suggest that TNF\u2010\u03b1 thus produced pioneers the proinflammatory signal during proteotoxic stress response with an important implication for inflammation and cancer.\u2014Ali, A., Biswas, A., Pal, M. HSF1 mediated TNF\u2010\u03b1 production during proteotoxic stress response pioneers proinflammatory signal in human cells. FASEB J. 33, 2621\u20132635 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801482r","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T14:02:04Z","timestamp":1539266524000},"page":"2621-2635","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["HSF1 mediated TNF\u2010\u03b1 production during proteotoxic stress response pioneers proinflammatory signal in human cells"],"prefix":"10.1096","volume":"33","author":[{"given":"Asif","family":"Ali","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine Bose Institute Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anindya","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Bose Institute Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahadeb","family":"Pal","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine Bose Institute Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.55.070186.005443"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1126\/science.1068408","article-title":"Molecular chaperones in the cytosol: from nascent chain to folded protein","volume":"295","author":"Hard F. 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