國家衛生研究院 NHRI:Item 3990099045/10287
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    题名: Characterization of the GNMT-HectH9-PREX2 tripartite relationship in the pathogenesis of hepatocellular carcinoma
    作者: Li, CH;Yen, CH;Chen, YF;Lee, KJ;Fang, CC;Zhang, X;Lai, CC;Huang, SF;Lin, HK;Arthur Chen, YM
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: The pathogenesis of hepatocellular carcinoma (HCC) involves many molecular pathways. Glycine N-methyltransferase (GNMT) is downregulated in almost all HCC and its gene knockout mice developed HCC with high penetrance. We identified PREX2, a novel PTEN inhibitor, as a GNMT-interacting protein. Such interaction enhanced degradation of PREX2 through an E3 ligase HectH9-mediated proteasomal ubiquitination pathway. Depletion of GNMT or HectH9 resulted in AKT activation in a PREX2 dependent manner and enhanced cell proliferation. An elevated PREX2 protein expression accompanied by activation of AKT was observed in the liver of Gnmt knockout mice. PREX2 protein expression was upregulated in 54.9% of human HCC samples, while its mRNA level was comparable in tumor and tumor-adjacent tissue, suggesting a post-translational alteration of PREX2 expression. Higher level of PREX2 in the tumor tissues was associated with poorer survival. These results reveal a novel mechanism in which GNMT participates in AKT signaling and HCC tumorigenesis by promoting HectH9-mediated PREX2 degradation. This article is protected by copyright. All rights reserved.
    日期: 2017-05
    關聯: International Journal of Cancer. 2017 May;140(10):2284-2297.
    Link to: http://dx.doi.org/10.1002/ijc.30652
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0020-7136&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000399313200012
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85016093669
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