title: Disruption of ATP binding destabilizes NPM/B23 and inhibits anti-apoptotic function.
abstract: Nucleophosmin/B23, a major nucleolar phosphoprotein, is overexpressed in actively proliferating cells. In this study, we demonstrate that B23 exclusively localizes in the nucleolus, whereas ATP depletion results in the redistribution of B23 throughout the whole nucleus and destabilizes B23 via caspase-3 mediated cleavage. Interestingly, ATP binding precedes PI(3,4,5)P(3) binding at lysine 263 and ATP binding mutants fail to restore the anti-apoptotic functions of B23 in PC12 cells. Thus, the ATP-B23 interaction is required for the stability of the B23 protein and regulates cell survival, confining B23 within the nucleolus in PC12 cells.
authors.affiliation: Department of Anatomy, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Joung Woo
authors.initials: JW
authors.lastname: Choi
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Lee
authors.forename: Jee-Yin
authors.initials: JY
authors.lastname: Ahn
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites; D001667:Binding, Competitive; D053148:Caspase 3 / Q000378:metabolism; D002466:Cell Nucleolus / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D004355:Drug Stability; D008239:Lysine / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D016716:PC12 Cells; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D009687:Nuclear Proteins; D018129:Phosphatidylinositol Phosphates; D011994:Recombinant Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; D000090243:Nucleophosmin; D000255:Adenosine Triphosphate; C505410:Casp3 protein, rat; D053148:Caspase 3; D008239:Lysine