Nucleophosmin is a binding partner of nucleostemin in human osteosarcoma cells.
Nucleostemin (NS) is expressed in the nucleoli of adult and embryonic stem cells and in many tumors and tumor-derived cell lines. In coimmunoprecipitation experiments, nucleostemin is recovered with the tumor suppressor p53, and more recently we have demonstrated that nucleostemin exerts its role in cell cycle progression via a p53-dependent pathway. Here, we report that in human osteosarcoma cells, nucleostemin interacts with nucleophosmin, a nucleolar protein believed to possess oncogenic potential. Nucleostemin (NS) and nucleophosmin (NPM) displayed an extremely high degree of colocalization in the granular component of the nucleolus during interphase, and both proteins associated with prenucleolar bodies in late mitosis before the reformation of nucleoli. Coimmunoprecipitation experiments revealed that NS and NPM co-reside in complexes, and yeast two-hybrid experiments confirmed that they are interactive proteins, revealing the NPM-interactive region to be the 46-amino acid N-terminal domain of NS. In bimolecular fluorescence complementation studies, bright nucleolar signals were observed, indicating that these two proteins directly interact in the nucleolus in vivo. These results support the notion that cell cycle regulatory proteins congress and interact in the nucleolus, adding to the emerging concept that this nuclear domain has functions beyond ribosome production.
Ma
Hanhui
H
Program in Cell Dynamics, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Pederson
Thoru
T
D001859:Bone Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D019204:GTP-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D000090243:Nucleophosmin; D012516:Osteosarcoma / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D002352:Carrier Proteins; C469949:GNL3 protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin; D019204:GTP-Binding Proteins