• 생명과학회지
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• 제19권4호
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• pp.436-441
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• 2009

B23/nucleophosmin은 핵인 단백질로서 외부 스트레스에 의해 핵인에서 핵으로 이동하게 된다. 이러한 세포 내 위치변화는 MDM2에 의한 p53단백질의 안정화에 영향을 미친다. 노화세포는 거대한 단일 핵인을 가지고 있으며, 외부 스트레스에 의해 p53 안정성이 감소한다. 그렇지만, 노화세포에서 어떠한 기전에 의해 p53의 불안정성이 증가하는 지는 아직 밝혀진 바가 없다. 따라서 본 연구에서는 노화세포에서 B23/nucleophosmin과 p53간의 상호 관련성을 조사하여 p53 안정성에 미치는 영향을 규명하고자 하였다. 본 연구에서는 IMR90세포주에 ras oncogene을 과발현시켜 노화세포를 유도하였다. 핵인 스트레스에 의해 노화세포 내 p53 단백질 발현은 감소하였으나, B23/nucleophosmin 단백질의 발현은 정상세포와 큰 차이가 없었다. 그렇지만, 두 단백질의 세포 내 위치는 노화세포에서 변화가 있었다. 즉, 정상세포와 달리, 노화세포에서는 스트레스에 의해 핵 내 p53발현이 증가하지 않았으며, B23/nucleophosmin은 핵 내로 이동하지 않고, 핵인에 그대로 머물러 있었다. 노화세포에서 MDM2와 p53간 상호결합이 안정적으로 유지된대 비하여, p53과 B23/nucleophosmin간의 상호결합은 감소하였다. 이러한 결과는 노화세포에서 핵인 스트레스에 의한 p53단백질의 안정성은 B23/nucleophosmin 결합이 감소하여 일어나는 것으로 해석된다.

• BMB Reports
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• 제41권12호
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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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• 제43권2호
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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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• 제45권3호
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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.