EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes.
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.
Squatrito
Massimo
M
European Institute of Oncology, 435 Via Ripamonti, 20141 Milan, Italy.
Mancino
Monica
M
Donzelli
Maddalena
M
Areces
Liliana B
LB
Draetta
Giulio F
GF
D016475:3T3 Cells / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D002466:Cell Nucleolus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D017434:Protein Structure, Tertiary; D012322:RNA Precursors / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012261:Ribonucleoproteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D046911:Macromolecular Substances; C101633:PA2G4 protein, human; D012322:RNA Precursors; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins