{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:37:40Z","timestamp":1777509460117,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,6,23]],"date-time":"2015-06-23T00:00:00Z","timestamp":1435017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"JSPS KAKENHI Grant-in-Aid for scientific Research (C)","award":["No. 26460339"],"award-info":[{"award-number":["No. 26460339"]}]},{"name":"the Program for Liaoning Excellent Talents in University","award":["No. LJQ2012067"],"award-info":[{"award-number":["No. LJQ2012067"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p>Azole antifungals directly inhibit enzymes for ergosterol biosynthesis, and this direct action is thought to underlie antifungal actions of these drugs. Recent studies showed that azoles alter expression of genes for various cellular functions. However, transcription factors regulated by azoles and their roles in antifungal actions remain poorly characterized. Using luciferase assay, we found that miconazole increased luciferase activity under the promoter containing the<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>response element (<jats:styled-content style=\"fixed-case\">CRE<\/jats:styled-content>) motif. This azole\u2010induced activation of<jats:styled-content style=\"fixed-case\">CRE<\/jats:styled-content>reporter was abolished in Atf1\u2010deficient cells, suggesting that azoles induce Atf1 activation. As Atf1 is activated by stress\u2010activated<jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content>kinase Sty1 upon various stressors, we examined its involvement. Azoles increased phosphorylation of Sty1 for its activation, and Sty1 deletion impaired azole\u2010induced<jats:styled-content style=\"fixed-case\">CRE<\/jats:styled-content>reporter activation. In contrast, deletion of Pyp1, a tyrosine phosphatase which negatively regulates Sty1, increased<jats:styled-content style=\"fixed-case\">CRE<\/jats:styled-content>reporter activation. In addition, cells deficient in Atf1 and stress\u2010activated<jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content>kinase pathway showed resistance to azoles, whereas cells lacking Pyp1 increased azole susceptibility, suggesting a critical role for azole\u2010induced activation of<jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content>kinase\u2010Atf1 pathway in antifungal actions of azoles. Collectively, these results suggest that azoles activate stress\u2010activated<jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content>kinase pathway, thereby facilitating Atf1\u2010mediated transcription for antifungal effects.<\/jats:p>","DOI":"10.1111\/gtc.12263","type":"journal-article","created":{"date-parts":[[2015,6,23]],"date-time":"2015-06-23T10:09:49Z","timestamp":1435054189000},"page":"695-705","source":"Crossref","is-referenced-by-count":6,"title":["Azoles activate Atf1\u2010mediated transcription through<scp>MAP<\/scp>kinase pathway for antifungal effects in fission yeast"],"prefix":"10.1111","volume":"20","author":[{"given":"Lingling","family":"Hu","sequence":"first","affiliation":[{"name":"Division of Pharmacology Kobe University Graduate School of Medicine Kobe 650\u20100017 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics School of Pharmacy China Medical University Shenyang 110122 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Hayafuji","sequence":"additional","affiliation":[{"name":"Division of Pharmacology Kobe University Graduate School of Medicine Kobe 650\u20100017 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Pharmacology Kobe University Graduate School of Medicine Kobe 650\u20100017 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Furuyashiki","sequence":"additional","affiliation":[{"name":"Division of Pharmacology Kobe University Graduate School of Medicine Kobe 650\u20100017 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.2.407"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0022-3565(24)38171-6","article-title":"Lovastatin\u2010induced proliferation inhibition and apoptosis in C6 glial cells","volume":"289","author":"Choi J.W.","year":"1999","journal-title":"J. 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