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

Thomas Grimm, Michael Hölzel, Michaela Rohrmoser, Thomas Harasim, Anastassia Malamoussi, Anita Gruber-Eber, Elisabeth Kremmer, Dirk Eick

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3030-3043
Number of pages14
JournalNucleic Acids Research
Volume34
Issue number10
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Dive into the research topics of 'Dominant-negative Pes1 mutants inhibit ribosomal RNA processing and cell proliferation via incorporation into the PeBoW-complex'. Together they form a unique fingerprint.

Cite this