{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T06:11:35Z","timestamp":1696399895798},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,1,29]],"date-time":"2014-01-29T00:00:00Z","timestamp":1390953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The nuclear localization signal (<jats:styled-content style=\"fixed-case\">NLS<\/jats:styled-content>)\u2010containing proteins <jats:styled-content style=\"fixed-case\">LEDGF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 localize to the nucleus in both the spinous and basal layers of the epidermis in psoriatic skin, where they function as transcription factors or co\u2010factors to activate epidermal keratinocytes (<jats:styled-content style=\"fixed-case\">KC<\/jats:styled-content>s). However, the mechanism underlying the localization of these proteins remains to be elucidated. We investigated the differential nucleocytoplasmic transport of <jats:styled-content style=\"fixed-case\">NLS<\/jats:styled-content>\u2010containing proteins as a potential pathogenic mechanism for psoriasis vulgaris. Nucleoporins play an important role in the Ran\u2010<jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>\u2010dependent nucleocytoplasmic transport of <jats:styled-content style=\"fixed-case\">NLS<\/jats:styled-content>\u2010containing proteins. We showed, using immunohistochemical staining, that the nucleoporins Ran\u2010binding protein 2 (Ran<jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>2) and Ran\u2010<jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>ase\u2010activating protein 1 (Ran<jats:styled-content style=\"fixed-case\">GAP<\/jats:styled-content>1) have greater expression on the nuclear envelope in psoriatic epidermal <jats:styled-content style=\"fixed-case\">KC<\/jats:styled-content>s than in <jats:styled-content style=\"fixed-case\">KC<\/jats:styled-content>s from healthy controls. We then studied the signalling pathways involved in the regulation of these proteins in HaCaT cells. The two major downstream pathways of epidermal growth factor receptor (<jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>) signalling activated in psoriatic <jats:styled-content style=\"fixed-case\">KC<\/jats:styled-content>s are the <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>\/Erk\/1\/2 and the phosphatidylinositol\u20103\u2010kinase\/Akt pathways. Therefore, we treated HaCaT cells with inhibitors to disrupt the <jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content> kinase kinase 1 (<jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>1), PI3\u2010kinase, or m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> pathways. Ran<jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>2 and Ran<jats:styled-content style=\"fixed-case\">GAP<\/jats:styled-content>1 protein expression levels were significantly greater in the nuclear envelope of HaCaT cells that were not treated with inhibitors than in cells treated with a combination of PI3\u2010kinase and <jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>1 inhibitors or m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>1 inhibitors. These results suggest that adequate nuclear envelope expression of RanBP2 and RanGAP1 could be a prerequisite for nucleocytoplasmic transport in <jats:styled-content style=\"fixed-case\">KC<\/jats:styled-content>s in psoriatic epidermis.<\/jats:p>","DOI":"10.1111\/exd.12324","type":"journal-article","created":{"date-parts":[[2014,1,18]],"date-time":"2014-01-18T08:12:49Z","timestamp":1390032769000},"page":"119-124","source":"Crossref","is-referenced-by-count":6,"title":["Nuclear envelope localization of <scp>R<\/scp>an\u2010binding protein 2 and <scp>R<\/scp>an\u2010<scp>GTP<\/scp>ase\u2010activating protein 1 in psoriatic epidermal keratinocytes"],"prefix":"10.1111","volume":"23","author":[{"given":"Kayo","family":"Yasuda","sequence":"first","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazumitsu","family":"Sugiura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Takeichi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinao","family":"Muro","sequence":"additional","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,1,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2005.06645.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1689"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2005.04.035"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.2003.00100.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2004.06088.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-4362.1999.00622.x"},{"key":"e_1_2_10_8_1","first-page":"357","volume-title":"Cytokine abnormalities in the 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