title: Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis.
abstract: p53 is a tumor suppressor gene whose regulation is crucial to maintaining genome stability and for the apoptotic elimination of abnormal, potentially cancer-predisposing cells. C. elegans contains a primordial p53 gene, cep-1, that acts as a transcription factor necessary for DNA damage-induced apoptosis. In a genetic screen for negative regulators of CEP-1, we identified a mutation in GLD-1, a translational repressor implicated in multiple C. elegans germ cell fate decisions and related to mammalian Quaking proteins. CEP-1-dependent transcription of proapoptotic genes is upregulated in the gld-1(op236) mutant and an elevation of p53-mediated germ cell apoptosis in response to DNA damage is observed. Further, we demonstrate that GLD-1 mediates its repressive effect by directly binding to the 3'UTR of cep-1/p53 mRNA and repressing its translation. This study reveals that the regulation of cep-1/p53 translation influences DNA damage-induced apoptosis and demonstrates the physiological importance of this mechanism.
authors.affiliation: Department of Cell Biology, Max-Planck-Institute for Biochemistry, Am Klopferspitz 18a, D 82152 Martinsried, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Schumacher
authors.forename: Momoyo
authors.initials: M
authors.lastname: Hanazawa
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Lee
authors.forename: Sudhir
authors.initials: S
authors.lastname: Nayak
authors.forename: Katrin
authors.initials: K
authors.lastname: Volkmann
authors.forename: E Randal
authors.initials: ER
authors.lastname: Hofmann
authors.forename: Randall
authors.initials: R
authors.lastname: Hofmann
authors.forename: Michael
authors.initials: M
authors.lastname: Hengartner
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
authors.forename: Anton
authors.initials: A
authors.lastname: Gartner
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001665:Binding Sites / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012733:Sex Differentiation / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C438244:CEP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C094448:GLD-1 protein, C elegans; D012333:RNA, Messenger; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53