title: p62 modulates the intrinsic signaling of UVB-induced apoptosis.
abstract: UVB radiation is the main source of sunburn and skin cancers. Apoptosis eliminates photodamaged cells, and is thus important for preventing epidermal carcinogenesis. The cytoplasmic regulatory protein p62/A170/sequestosome 1 (p62) molecule is involved in a variety of cellular and signaling pathways. p62 is known to be and important in autophagy, but its role in UVB-induced apoptosis remains to be clarified.
  
  
  
  To investigate the role of p62 against UVB-induced apoptotic changes, using mouse embryonic fibroblasts (MEFs) derived from p62 homozygous knockout (p62(-/-)) mice.
  
  
  
  p62(-/-) and wild-type (p62(+/+)) mice and MEFs were subjected to UVB irradiation, and the resultant apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blots.
  
  
  
  Apoptosis was decreased in the p62(-/-) MEFs compared to p62(+/+) MEFs in response to UVB treatment. Compared with p62(+/+) MEFs, p62(-/-) MEFs expressed significantly more Bcl-2 and less Bax, and showed increased Src and Stat3 phosphorylation. Our results show that p62 regulates apoptotic pathways by modifying critical signaling intermediates such as Src and Stat3.
  
  
  
  p62 deficiency [corrected] reduces UVB-induced apoptosis by modulating intrinsic apoptotic signaling through Src phosphorylation.
authors.affiliation: Plastic and Reconstructive Surgery, Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba. Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ito
authors.affiliation: Environmental Molecular Biology, Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba. Tsukuba, Ibaraki, 305-8575 Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Department of Environmental Molecular Biology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Warabi
authors.affiliation: Department of Dermatology, Tokyo Medical University Ibaraki Medical Center, Ami, Inashiki, Ibaraki 300-0395, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawachi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamatoji
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Uchida
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Ishibashi-Kanno
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Medical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Shoda
authors.affiliation: Department of Neurophysiology, Faculty of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Tabuchi
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki305-8575, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Bukawa
authors.affiliation: Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sekido
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. Electronic address: ytony@md.tsukuba.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Yanagawa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects; D005838:Genotype; D018345:Mice, Knockout; D010641:Phenotype; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071456:Sequestosome-1 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; C494087:Stat3 protein, mouse; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D019061:src-Family Kinases
keywords: Apoptosis; ROS; UVB; p62