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    National Tsing Hua University Institutional Repository > 生命科學院  > 生命科學系 > 期刊論文 >  The antagonism between MCT-1 and p53 affects the tumorigenic outcomes


    Please use this identifier to cite or link to this item: http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/81447


    Title: The antagonism between MCT-1 and p53 affects the tumorigenic outcomes
    Authors: Ravi Kasiappan;Hung-Ju Shih;Meng-Hsun Wu;ChikOn Choy;Tai-Du Lin;Linyi Chen;Hsin-Ling Hsu
    教師: 陳令儀
    Date: 2010
    Publisher: BioMed Central
    Relation: Molecular Cancer, BioMed Central, Volume 9, 311, DEC 2010, Pages 17
    Keywords: POLYMERASE-III TRANSCRIPTION
    FACTOR-BINDING-SITES
    TUMOR-SUPPRESSOR
    CANDIDATE ONCOGENE
    NEGATIVE REGULATOR
    CELL
    CANCER
    PROMOTES
    PROTEIN
    MDM2
    Abstract: Background
    MCT-1 oncoprotein accelerates p53 protein degradation via a proteosome pathway. Synergistic promotion of the xenograft tumorigenicity has been demonstrated in circumstance of p53 loss alongside MCT-1 overexpression. However, the molecular regulation between MCT-1 and p53 in tumor development remains ambiguous. We speculate that MCT-1 may counteract p53 through the diverse mechanisms that determine the tumorigenic outcomes.

    Results
    MCT-1 has now identified as a novel target gene of p53 transcriptional regulation. MCT-1 promoter region contains the response elements reactive with wild-type p53 but not mutant p53. Functional p53 suppresses MCT-1 promoter activity and MCT-1 mRNA stability. In a negative feedback regulation, constitutively expressed MCT-1 decreases p53 promoter function and p53 mRNA stability. The apoptotic events are also significantly prevented by oncogenic MCT-1 in a p53-dependent or a p53-independent fashion, according to the genotoxic mechanism. Moreover, oncogenic MCT-1 promotes the tumorigenicity in mice xenografts of p53-null and p53-positive lung cancer cells. In support of the tumor growth are irrepressible by p53 reactivation in vivo, the inhibitors of p53 (MDM2, Pirh2, and Cop1) are constantly stimulated by MCT-1 oncoprotein.

    Conclusions
    The oppositions between MCT-1 and p53 are firstly confirmed at multistage processes that include transcription control, mRNA metabolism, and protein expression. MCT-1 oncogenicity can overcome p53 function that persistently advances the tumor development.
    Relation Link: http://www.biomedcentral.com/
    URI: http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/81447
    Appears in Collections:[生命科學系] 期刊論文
    [分子醫學研究所] 期刊論文
    [腦科學研究中心] 期刊論文

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