title: p53 Is a Direct Transcriptional Repressor of Keratin 17: Lessons from a Rat Model of Radiation Dermatitis.
abstract: The intermediate filament protein keratin 17 (Krt17) shows highly dynamic and inducible expression in skin physiology and pathology. Because Krt17 exerts physiologically important functions beyond providing structural stability to keratinocytes whereas abnormal Krt17 expression is a key feature of dermatoses such as psoriasis and pachyonychia congenita, the currently unclear regulation of Krt17 expression needs to be better understood. Using a rat model of radiation dermatitis, we report here that Krt17 expression initially is down-regulated but later is strongly up-regulated by ionizing radiation. The early down-regulation correlates with the activation of p53 signaling. Deletion of p53 abolishes the initial down-regulation but not its subsequent up-regulation, suggesting that p53 represses Krt17 transcription. Because previous work reported up-regulation of Krt17 by ultraviolet irradiation, which also activates p53 signaling, the effect of ultraviolet radiation was reexamined. This revealed that the initial down-regulation of Krt17 is conserved, but the up-regulation comes much faster. Chromatin immunoprecipitation analysis in vivo and electromobility shift assay in vitro identified two p53-binding sites in the promoter region of Krt17. Thus, p53 operates as a direct Krt17 repressor, which invites therapeutic targeting in dermatoses characterized by excessive Krt17 expression.
authors.affiliation: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liao
authors.affiliation: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian, China.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Haijie
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, China. Electronic address: benhuaxu@163.com.
authors.forename: Benhua
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.affiliation: Dermatology Research Centre, Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom; Department of Dermatology, University of Muenster, Muenster, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
authors.affiliation: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian, China. Electronic address: zyue@fzu.edu.cn.
authors.forename: Zhicao
authors.initials: Z
authors.lastname: Yue
mesh_terms: D000818:Animals; D004249:DNA Damage; D004195:Disease Models, Animal; D015536:Down-Regulation; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007633:Keratins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011855:Radiodermatitis / Q000235:genetics* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C118917:Krt17 protein, mouse; D016159:Tumor Suppressor Protein p53; D007633:Keratins