title: Miz-1 regulates translation of Trp53 via ribosomal protein L22 in cells undergoing V(D)J recombination.
abstract: To be effective, the adaptive immune response requires a large repertoire of antigen receptors, which are generated through V(D)J recombination in lymphoid precursors. These precursors must be protected from DNA damage-induced cell death, however, because V(D)J recombination generates double-strand breaks and may activate p53. Here we show that the BTB/POZ domain protein Miz-1 restricts p53-dependent induction of apoptosis in both pro-B and DN3a pre-T cells that actively rearrange antigen receptor genes. Miz-1 exerts this function by directly activating the gene for ribosomal protein L22 (Rpl22), which binds to p53 mRNA and negatively regulates its translation. This mechanism limits p53 expression levels and thus contains its apoptosis-inducing functions in lymphocytes, precisely at differentiation stages in which V(D)J recombination occurs.
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7; Division of Experimental Medicine, McGill University, Montréal, QC, Canada H3A 1A3;
authors.forename: Marissa
authors.initials: M
authors.lastname: Rashkovan
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7;
authors.forename: Charles
authors.initials: C
authors.lastname: Vadnais
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7; Division of Experimental Medicine, McGill University, Montréal, QC, Canada H3A 1A3;
authors.forename: Julie
authors.initials: J
authors.lastname: Ross
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7;
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gigoux
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7;
authors.forename: Woong-Kyung
authors.initials: WK
authors.lastname: Suh
authors.affiliation: Institute for Cancer Genetics and Department of Pathology and Cell Biology, Columbia University, New York, NY 10032;
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: Center for Molecular Biomedicine, Friedrich Schiller University Jena, 07743 Jena, Germany; and.
authors.forename: Christian
authors.initials: C
authors.lastname: Kosan
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7; Division of Experimental Medicine, McGill University, Montréal, QC, Canada H3A 1A3; Département de Microbiologie, Infectiologie, et Immunologie, Université de Montréal, Montreal, QC, Canada H3C 3J7 tarik.moroy@ircm.qc.ca.
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016923:Cell Death / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics; D015151:Immunoblotting; D047468:Immunoprecipitation; D054503:Lymphoid Progenitor Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics / Q000502:physiology*; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D060152:V(D)J Recombination / Q000235:genetics* / Q000502:physiology
chemical_list: D009687:Nuclear Proteins; D050828:Protein Inhibitors of Activated STAT; D016601:RNA-Binding Proteins; C522051:RPL22 protein, mouse; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C485521:Miz1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Miz-1; Rpl22; V(D)J recombination; p53