國家衛生研究院 NHRI:Item 3990099045/2792
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2792


    Title: Phosphorylation of p53 on Thr55 by ERK2 is necessary for doxorubicin-induced p53 activation and cell death
    Authors: Yeh, PY;Chuang, SE;Yeh, KH;Song, YC;Chang, LLY;Cheng, AL
    Contributors: National Institute of Cancer Research
    Abstract: We recently reported that exposure of human cervical carcinoma cells to doxorubicin results in extracellular signal-regulated kinase (ERK) 2 activation, which in turn phosphorylates p53 on a previously uncharacterized site, Thr55. This study sought to clarify the biological significance of doxorubicin-induced Thr55 phosphorylation. In breast carcinoma MCF7 cells, doxorubicin (300 nM) activated ERK2 and induced phosphorylation of p53 on Thr55 residues. Pretreatment of MCF7 cells with an ERK2 chemical inhibitor, PD98059 or U0126, blocked doxorubicin-induced p53 activation and suppressed phosphorylation of p53Thr55. MCF55a cells were established by transfection of full-length p53 carrying Thr55 mutation (Thr to Ala) into MCF7 cells. Doxorubicin ( 500 nM) could not induce p53 activation in MCF55a cells, which showed significantly increased drug resistance toward doxorubicin. While the expression of the apoptotic protein, Bax, showed no difference between MCF7 and MCF55a cells, Bcl-2, an antiapoptotic protein, was constitutively expressed in MCF55a cells. The increase of Bcl-2 protein and/or Bcl-2/Bax ratio might at least partly contribute to the drug resistance of MCF55a cells. In summary, our results suggest that phosphorylation of p53Thr55 by ERK2 is important for doxorubicin-induced p53 activation and cell death.
    Keywords: Biochemistry & Molecular Biology;Oncology;Cell Biology;Genetics & Heredity
    Date: 2004-04-29
    Relation: Oncogene. 2004 Apr;23(20):3580-3588.
    Link to: http://dx.doi.org/10.1038/sj.onc.1207426
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0950-9232&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000221101700009
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=2442639165
    Appears in Collections:[Shuang-En Chuang] Periodical Articles

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