Mammalian WDR12 is a novel member of the Pes1-Bop1 complex and is required for ribosome biogenesis and cell proliferation

• Published in: The Journal of cell biology Vol. 170; no. 3; pp. 367 - 378
• Main Authors: Hölzel, Michael, Rohrmoser, Michaela, Schlee, Martin, Grimm, Thomas, Harasim, Thomas, Malamoussi, Anastassia, Gruber-Eber, Anita, Kremmer, Elisabeth, Hiddemann, Wolfgang, Bornkamm, Georg W, Eick, Dirk
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 01.08.2005; The Rockefeller University Press
• Subjects: Animals; B lymphocytes; Cell cycle; Cell growth; Cell Line; Cell lines; Cell Proliferation; Cellular biology; Cyclin-Dependent Kinase Inhibitor p16; Delta cells; Fibroblasts; Gene expression; HEK293 cells; Hepatocytes; Humans; Mammals; Mice; Mutation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Protein Binding; Proteins - metabolism; Proto-Oncogene Proteins c-myc - metabolism; Rats; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Ribonucleic acid; Ribosomes; Ribosomes - metabolism; RNA; RNA, Ribosomal - metabolism; S Phase - physiology; Tumor Suppressor Protein p14ARF - metabolism; Tumor Suppressor Protein p53 - biosynthesis; Tumor Suppressor Protein p53 - genetics; Yeasts
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200501141

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.