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Dominant-negative Pes1 mutants inhibit ribosomal RNA processing and cell proliferation via incorporation into the PeBoW-complex.

Nucleic Acids Res. 34, 3030-3043 (2006)
Verlagsversion Volltext DOI
Open Access Gold
Creative Commons Lizenzvertrag
The nucleolar PeBoW-complex, consisting of Pes1, Bop1 and WDR12, is essential for cell proliferation and processing of ribosomal RNA in mammalian cells. Here we have analysed the physical and functional interactions of Pes1 deletion mutants with the PeBoW-complex. Pes1 mutants M1 and M5, with N- and C-terminal truncations, respectively, displayed a dominant-negative phenotype. Both mutants showed nucleolar localization, blocked processing of the 36S/32S precursors to mature 28S rRNA, inhibited cell proliferation, and induced high p53 levels in proliferating, but not in resting cells. Mutant M1 and M5 proteins associated with large pre-ribosomal complexes and co-immunoprecipitated Bop1 and WDR12 proteins indicating their proper incorporation into the PeBoW-complex. We conclude that the dominant-negative effect of the M1 and M5 mutants is mediated by the impaired function of the PeBoW-complex.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter TUMOR-SUPPRESSOR P53; PROTEIN L11; MAMMALIAN-CELLS; C-MYC; BIOGENESIS; CYCLE; INACTIVATION; PESCADILLO; PATHWAY; HDM2
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Quellenangaben Band: 34, Heft: 10, Seiten: 3030-3043 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus