EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes

被引:111
作者
Squatrito, M [1 ]
Mancino, M [1 ]
Donzelli, M [1 ]
Areces, LB [1 ]
Draetta, GF [1 ]
机构
[1] European Inst Oncol, I-20141 Milan, Italy
关键词
rRNA; nucleolus; growth control; localization signal; proteohics; ribosome assembly;
D O I
10.1038/sj.onc.1207579
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
EBP1 was identified as a protein that interacts with the ErbB-3 receptor and possibly contributes to transducing growth regulatory signals. The existence of EBP1 homologs across species from simple eukaryotes to humans and its wide tissue expression pattern suggest that EBP1 acts as a general signaling molecule. We provide evidence that EBP1 is localized to the cytoplasm and to the nucleolus, and that its nucleolar localization requires amino-acid sequences present at both the amino- and carboxy-terminus of the molecule. We also show that EBP1 overexpression inhibits proliferation of human fibroblasts, and that this effect is linked to its nucleolar localization. Using mass spectrometry we demonstrate that EBP1 is part of ribonucleoprotein complexes and associates with different rRNA species. It is becoming clear that cell growth and proliferation are actively coordinated with rRNA processing and ribosome assembly. Our findings indicate that EBP1 is a nucleolar growth-regulating protein, and we propose that it could represent a new link between ribosome biosynthesis and cell proliferation.
引用
收藏
页码:4454 / 4465
页数:12
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