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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)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
TUMOR-SUPPRESSOR P53; PROTEIN L11; MAMMALIAN-CELLS; C-MYC; BIOGENESIS; CYCLE; INACTIVATION; PESCADILLO; PATHWAY; HDM2
Language
english
Publication Year
2006
HGF-reported in Year
0
ISSN (print) / ISBN
0305-1048
e-ISSN
1362-4962
Journal
Nucleic Acids Research
Quellenangaben
Volume: 34,
Issue: 10,
Pages: 3030-3043
Publisher
Oxford University Press
Reviewing status
Peer reviewed
Institute(s)
Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
Institute of Molecular Immunology (IMI)
Institute of Molecular Immunology (IMI)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s)
G-501400-001
G-501700-003
G-501700-003
PubMed ID
16738141
WOS ID
000239430900018
Scopus ID
33745137485
Erfassungsdatum
2006-09-26