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

Dominant-negative Pes1 mutants inhibit ribosomal RNA processing and cell proliferation via incorporation into the PeBoW-complex.
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DOI:
10.1093/nar/gkl378
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发表时间:
2006
影响因子:
14.9
通讯作者:
Eick D
Eick D
中科院分区:
生物学2区
文献类型:
--
作者:
Grimm T;Hölzel M;Rohrmoser M;Harasim T;Malamoussi A;Gruber-Eber A;Kremmer E;Eick D

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核仁pebow复合体由Pes1、Bop1和WDR12组成,在哺乳动物细胞中对细胞增殖和核糖体RNA加工至关重要。在这里,我们分析了Pes1缺失突变体与pebow复合物的物理和功能相互作用。Pes1突变体M1和M5分别具有N端和c端截断,表现为显性阴性表型。这两种突变体都显示出核核定位,阻断了36S/32S前体向成熟28S rRNA的加工,抑制了细胞增殖,并在增殖细胞中诱导了高水平的p53,但在静息细胞中没有。突变的M1和M5蛋白与大型核糖体前复合物和共免疫沉淀的Bop1和WDR12蛋白相关,表明它们正确地结合到pebow复合物中。我们得出结论,M1和M5突变体的显性负作用是由pebow复合物的功能受损介导的。
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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发表时间: 2005-01-20
影响因子: 158.5
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