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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,9,19]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    UV tanning is a common social behavior, which increases melanin production and pigmentation of the skin. UV irradiation is a standard treatment of depigmenting diseases such as vitiligo. However, recurrent UV irradiation is genotoxic and facilitates skin aging and cancer. Here, we identified a method of inducing hyperpigmentation by inhibition of casein kinase 1\u03b1 (CK1\u03b1). UV tanning is induced through activation of p53, via the Pomc\/\u03b1-MSH\/Mc1r\/Mitf pathway, but both\n                    <jats:italic>Pomc<\/jats:italic>\n                    and\n                    <jats:italic>Mc1r<\/jats:italic>\n                    function can be compromised by aging or allelic polymorphism. In contrast, inhibition of CK1\u03b1 activates a different pathway, p53\/KitL\/Kit, and raises protective eumelanin without the procarcinogenic pheomelanin. Inhibition of CK1\u03b1 is therefore expected to be an effective strategy for skin protection from sunlight and for treating depigmenting diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1702763114","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T00:29:57Z","timestamp":1504744197000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":35,"title":["CK1\u03b1 ablation in keratinocytes induces p53-dependent, sunburn-protective skin hyperpigmentation"],"prefix":"10.1073","volume":"114","author":[{"given":"Chung-Hsing","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Dermatology, China Medical University Hospital, Taichung 40447, Taiwan;"},{"name":"Department of Dermatology, China Medical University, Taichung 40447, Taiwan;"},{"name":"Skin Institute, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan;"},{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan;"},{"name":"Research Center for Applied Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che-Jung","family":"Kuo","sequence":"additional","affiliation":[{"name":"National Laboratory Animal Center\u2013Tainan Facility, National Applied Research Laboratories, Tainan City 74147, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamichi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Dermatology, China Medical University Hospital, Taichung 40447, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ya","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Dermatology, China Medical University Hospital, Taichung 40447, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Tse","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Laboratory Animal Center\u2013Tainan Facility, National Applied Research Laboratories, Tainan City 74147, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hsi","family":"Chiu","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hsiung","family":"Lin","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Nist","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Genomics Core Facility, Center for Tumor and Immunobiology, Philipps-University Marburg, 35037 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mernberger","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Genomics Core 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Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-An","family":"Hsueh","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheau-Yann","family":"Shieh","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irit","family":"Snir-Alkalay","sequence":"additional","affiliation":[{"name":"The Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel\u2013Canada, Hebrew University\u2013Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinon","family":"Ben-Neriah","sequence":"additional","affiliation":[{"name":"The Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel\u2013Canada, Hebrew University\u2013Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,9,6]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nchembio.1548","article-title":"Multifaceted pathways protect human skin from UV radiation","volume":"10","author":"Natarajan VT","year":"2014","unstructured":"VT Natarajan, P Ganju, A Ramkumar, R Grover, RS Gokhale, Multifaceted pathways protect human skin from UV radiation. 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FASEB J 21, 976\u2013994 (2007).","journal-title":"FASEB J"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.cell.2006.12.045","article-title":"Central role of p53 in the suntan response and pathologic hyperpigmentation","volume":"128","author":"Cui R","year":"2007","unstructured":"R Cui, , Central role of p53 in the suntan response and pathologic hyperpigmentation. Cell 128, 853\u2013864 (2007).","journal-title":"Cell"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1152\/physrev.00044.2003","article-title":"Melanin pigmentation in mammalian skin and its hormonal regulation","volume":"84","author":"Slominski A","year":"2004","unstructured":"A Slominski, DJ Tobin, S Shibahara, J Wortsman, Melanin pigmentation in mammalian skin and its hormonal regulation. 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J Biol Chem 284, 4343\u20134353 (2009).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/pcmr.12063","article-title":"Endothelin-1 is a transcriptional target of p53 in epidermal keratinocytes and regulates ultraviolet-induced melanocyte homeostasis","volume":"26","author":"Hyter S","year":"2013","unstructured":"S Hyter, , Endothelin-1 is a transcriptional target of p53 in epidermal keratinocytes and regulates ultraviolet-induced melanocyte homeostasis. 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