B23 and ARF: friends or foes?
B23 (nucleophosmin/NPM) is a multifunctional protein that recently has been directly implicated in the p53 network by its documented interaction with the p14(ARF)/p19(Arf) tumor suppressor, a major upstream activator of p53. Here we provide an overview of the functional interactions of B23 and ARF. We also integrate the current models into a unified picture, showing that B23 is essential for stabilizing and maintaining a basal level of ARF in the nucleolus, whereas increasing levels of ARF after oncogenic stress promotes B23 degradation and interferes with B23 nucleocytoplasmic shuttling. In this way, ARF can be regarded as a parasitic peptide on the B23 molecule, because ARF uses this chaperone for its own survival but also antagonizes normal activities of B23. Finally, the functional significance of the ARF-B23 interaction for tumor development and the prospects for novel cancer therapies are evaluated.
Lindström
Mikael S
MS
Department of Radiation Oncology and Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7512, USA.
Zhang
Yanping
Y
D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000090243:Nucleophosmin; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D014178:Translocation, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin; D051736:Proto-Oncogene Proteins c-mdm2