• Journal of Life Science
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• v.19 no.4
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• pp.436-441
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• 2009

B23/nucleophosmin, a nucleolar protein, translocates into the nucleus from the nucleolus when cells are damaged by extracellular stresses. Recently, it was shown that such translocation of B23/nucleophosmin in normal fibroblasts under stress conditions increases both the stability and activation of the p53 protein by disrupting its interaction with MDM2. Senescent cells have a single large nucleolus and a diminished capacity to induce p53 stability upon exposure to various DNA damaging agents. To investigate the role of B23/nucleophosmin in p53 stability in senescent cells, we established a senescence model system by expressing the ras oncogene in IMR90 cells. The stability of p53 was reduced in these cells in response to nucleolar stress, although the level of B23/nucleophosmin protein was not changed. In addition, p53 did not accumulate in the nucleus and B23/nucleophosmin did not translocate into the nucleoplasm. The binding affinity of B23/nucleophosmin with p53 was reduced in senescent cells, whereas the interaction between MDM2 and p53 was stable. Taken together, the stability of p53 in ras-induced senescent cells may be influenced by the ability of B23/nucleophosmin to interact with p53 in response to nucleolar stress.

• BMB Reports
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• v.41 no.12
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• pp.840-845
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• 2008

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)P3 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.

• BMB Reports
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• v.43 no.2
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• pp.127-132
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• 2010

Phosphatidylinositol (3,4,5)-triphosphate ($PIP_3$) is a lipid second messenger that employs a wide range of downstream effector proteins for the regulation of cellular processes, including cell survival, polarization and proliferation. One of the most well characterized cytoplasmic targets of $PIP_3$, serine/threonine protein kinase B (PKB)/Akt, promotes cell survival by directly interacting with nucleophosmin (NPM)/B23, the nuclear target of $PIP_3$. Here, we report that nuclear $PIP_3$ competes with Akt to preferentially bind B23 in the nucleoplasm. Mutation of Arg23 and Arg25 in the PH domain of Akt prevents binding to $PIP_3$, but does not disrupt the Akt/B23 interaction. However, treatment with phosphatases PTEN or SHIP abrogates the association between Akt and B23, indicating that nuclear $PIP_3$ regulates the Akt/B23 interaction by controlling the concentration and subcellular dynamics of these two proteins.

• Parasites, Hosts and Diseases
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• v.45 no.3
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• pp.165-174
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• 2007

Toxoplasma gondii GRA10 expressed as a GFP-GRA10 fusion protein in HeLa cells moved to the nucleoli within the nucleus rapidly and entirely. GRA10 was concentrated specifically in the dense fibrillar component of the nucleolus morphologically by the overlap of GFP-GRA10 transfection image with IFA images by monoclonal antibodies against GRA10 (Tg378), B23 (nucleophosmin) and C23 (nucleolin). The nucleolar translocalization of GRA10 was caused by a putative nucleolar localizing sequence (NoLS) of GRA10. Interaction of GRA10 with TATA-binding protein associated factor 1B (TAF1B) in the yeast two-hybrid technique was confirmed by GST pull-down assay and immunoprecipitation assay. GRA10 and TAF1B were also co-localized in the nucleolus after co-transfection. The nucleolar condensation of GRA10 was affected by actinomycin D. Expressed GFP-GRA10 was evenly distributed over the nucleoplasm and the nucleolar locations remained as hollows in the nucleoplasm under a low dose of actinomycin D. Nucleolar localizing and interacting of GRA10 with TAF1B suggested the participation of GRA10 in rRNA synthesis of host cells to favor the parasitism of T. gondii.