title: Mammalian WDR12 is a novel member of the Pes1-Bop1 complex and is required for ribosome biogenesis and cell proliferation.
abstract: Target genes of the protooncogene c-myc are implicated in cell cycle and growth control, yet the linkage of both is still unexplored. Here, we show that the products of the nucleolar target genes Pes1 and Bop1 form a stable complex with a novel member, WDR12 (PeBoW complex). Endogenous WDR12, a WD40 repeat protein, is crucial for processing of the 32S precursor ribosomal RNA (rRNA) and cell proliferation. Further, a conditionally expressed dominant-negative mutant of WDR12 also blocks rRNA processing and induces a reversible cell cycle arrest. Mutant WDR12 triggers accumulation of p53 in a p19ARF-independent manner in proliferating cells but not in quiescent cells. Interestingly, a potential homologous complex of Pes1-Bop1-WDR12 in yeast (Nop7p-Erb1p-Ytm1p) is involved in the control of ribosome biogenesis and S phase entry. In conclusion, the integrity of the PeBoW complex is required for ribosome biogenesis and cell proliferation in mammalian cells.
authors.affiliation: Institute of Clinical Molecular Biology and Tumour Genetics, National Research Center for Environment and Health (GSF), 81377 Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hölzel
authors.forename: Michaela
authors.initials: M
authors.lastname: Rohrmoser
authors.forename: Martin
authors.initials: M
authors.lastname: Schlee
authors.forename: Thomas
authors.initials: T
authors.lastname: Grimm
authors.forename: Thomas
authors.initials: T
authors.lastname: Harasim
authors.forename: Anastassia
authors.initials: A
authors.lastname: Malamoussi
authors.forename: Anita
authors.initials: A
authors.lastname: Gruber-Eber
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Georg W
authors.initials: GW
authors.lastname: Bornkamm
authors.forename: Dirk
authors.initials: D
authors.lastname: Eick
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16; D006801:Humans; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism; D016601:RNA-Binding Proteins; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D016196:S Phase / Q000502:physiology; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: C488958:Bop1 protein, mouse; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; C484463:PES1 protein, human; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin