title: Piwil2 inhibits keratin 8 degradation through promoting p38-induced phosphorylation to resist Fas-mediated apoptosis.
abstract: The piwi-like 2 (piwil2) gene is widely expressed in tumors and protects cells from apoptosis induced by a variety of stress stimuli. However, the role of Piwil2 in Fas-mediated apoptosis remains unknown. Here, we present evidence that Piwil2 inhibits Fas-mediated apoptosis. By a bacterial two-hybrid screening, we identify a new Piwil2-interacting partner, keratin 8 (K8), a major intermediate filament protein protecting the cell from Fas-mediated apoptosis. Our results show that Piwil2 binds to K8 and p38 through its PIWI domain and forms a Piwil2/K8/P38 triple protein-protein complex. Thus, Piwil2 increases the phosphorylation level of K8 Ser-73 and then inhibits ubiquitin-mediated degradation of K8. As a result, the knockdown of Piwil2 increases the Fas protein level at the membrane. In addition to our previous finding that Piwil2 inhibits the expression of p53 through the Src/STAT3 pathway, here we demonstrate that Piwil2 represses p53 phosphorylation through p38. Our present study indicates that Piwil2 plays a role in Fas-mediated apoptosis for the first time and also can affect p53 phosphorylation in tumor cells, revealing a novel mechanism of Piwil2 in apoptosis, and supports that Piwil2 plays an active role in tumorigenesis.
authors.affiliation: Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Lianfang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yilu
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Dachang
authors.initials: D
authors.lastname: Tao
authors.affiliation: Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yunqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Huaqin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Sizhong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China mayongxin@gmail.com.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Ma
mesh_terms: D017209:Apoptosis; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D053533:Keratin-8 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D060565:Argonaute Proteins; C491901:FAS protein, human; C426203:KRT8 protein, human; D053533:Keratin-8; C486868:PIWIL2 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D012694:Serine; D048051:p38 Mitogen-Activated Protein Kinases
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