title: p53 acts as a safeguard of translational control by regulating fibrillarin and rRNA methylation in cancer.
abstract: Ribosomes are specialized entities that participate in regulation of gene expression through their rRNAs carrying ribozyme activity. Ribosome biogenesis is overactivated in p53-inactivated cancer cells, although involvement of p53 on ribosome quality is unknown. Here, we show that p53 represses expression of the rRNA methyl-transferase fibrillarin (FBL) by binding directly to FBL. High levels of FBL are accompanied by modifications of the rRNA methylation pattern, impairment of translational fidelity, and an increase of internal ribosome entry site (IRES)-dependent translation initiation of key cancer genes. FBL overexpression contributes to tumorigenesis and is associated with poor survival in patients with breast cancer. Thus, p53 acts as a safeguard of protein synthesis by regulating FBL and the subsequent quality and intrinsic activity of ribosomes.
authors.affiliation: Centre de Recherche en Cancérologie de Lyon UMR Inserm 1052 CNRS 5286, Centre Léon Bérard, F-69373, Lyon, France; Université de Lyon, Université Lyon 1, ISPB, Lyon F-69622, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Marcel
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Ghayad
authors.forename: Stéphane
authors.initials: S
authors.lastname: Belin
authors.forename: Gabriel
authors.initials: G
authors.lastname: Therizols
authors.forename: Anne-Pierre
authors.initials: AP
authors.lastname: Morel
authors.forename: Eduardo
authors.initials: E
authors.lastname: Solano-Gonzàlez
authors.forename: Julie A
authors.initials: JA
authors.lastname: Vendrell
authors.forename: Sabine
authors.initials: S
authors.lastname: Hacot
authors.forename: Hichem C
authors.initials: HC
authors.lastname: Mertani
authors.forename: Marie Alexandra
authors.initials: MA
authors.lastname: Albaret
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Bourdon
authors.forename: Lee
authors.initials: L
authors.lastname: Jordan
authors.forename: Alastair
authors.initials: A
authors.lastname: Thompson
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Tafer
authors.forename: Rong
authors.initials: R
authors.lastname: Cong
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouvet
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Saurin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Catez
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Prats
authors.forename: Alain
authors.initials: A
authors.lastname: Puisieux
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Diaz
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008745:Methylation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D010442:Peptide Chain Initiation, Translational; D011379:Prognosis; D011485:Protein Binding; D014176:Protein Biosynthesis; D012335:RNA, Ribosomal / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D012335:RNA, Ribosomal; D016159:Tumor Suppressor Protein p53; C047458:fibrillarin
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