國家衛生研究院 NHRI:Item 3990099045/7752
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    題名: JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1alpha-mediated glucose metabolism
    其他題名: JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α-mediated glucose metabolism
    作者: Wang, HJ;Hsieh, YJ;Cheng, WC;Lin, CP;Lin, YS;Yang, SF;Chen, CC;Izumiya, Y;Yu, JS;Kung, HJ;Wang, WC
    貢獻者: Institute of Molecular and Genomic Medicine
    摘要: JMJD5, a Jumonji C domain-containing dioxygenase, is important for embryonic development and cancer growth. Here, we show that JMJD5 is up-regulated by hypoxia and is crucial for hypoxiainduced cell proliferation. JMJD5 interacts directly with pyruvate kinase muscle isozyme (PKM)2 to modulate metabolic flux in cancer cells. The JMJD5-PKM2 interaction resides at the intersubunit interface region of PKM2, which hinders PKM2 tetramerization and blocks pyruvate kinase activity. This interaction also influences translocation of PKM2 into the nucleus and promotes hypoxiainducible factor (HIF)-1α-mediated transactivation. JMJD5 knockdown inhibits the transcription of the PKM2-HIF-1α target genes involved in glucose metabolism, resulting in a reduction of glucose uptake and lactate secretion in cancer cells. JMJD5, along with PKM2 and HIF-1α, is recruited to the hypoxia response element site in the lactate dehydrogenase A and PKM2 loci and mediates the recruitment of the latter two proteins. Our data uncover a mechanism whereby PKM2 can be regulated by factor-binding- induced homo/heterooligomeric restructuring, paving the way to cell metabolic reprogram.
    日期: 2014-01-07
    關聯: Proceedings of the National Academy of Sciences of the United States of America. 2014 Jan 7;111(1):279-284.
    Link to: http://dx.doi.org/10.1073/pnas.1311249111
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8424&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000329350700076
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84891953688
    顯示於類別:[龔行健] 期刊論文
    [王鴻俊] 期刊論文

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