國家衛生研究院 NHRI:Item 3990099045/8643
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/8643


    Title: Skp2-MacroH2A1-CDK8 axis orchestrates G2/M transition and tumorigenesis
    Authors: Xu, D;Li, CF;Zhang, X;Gong, Z;Chan, CH;Lee, SW;Jin, G;Rezaeian, AH;Han, F;Wang, J;Yang, WL;Feng, ZZ;Chen, W;Wu, CY;Wang, YJ;Chow, LP;Zhu, XF;Zeng, YX;Lin, HK
    Contributors: National Institute of Cancer Research
    Abstract: Understanding the mechanism by which cell growth, migration, polyploidy, and tumorigenesis are regulated may provide important therapeutic strategies for cancer therapy. Here we identify the Skp2-macroH2A1 (mH2A1)-cyclin-dependent kinase 8 (CDK8) axis as a critical pathway for these processes, and deregulation of this pathway is associated with human breast cancer progression and patient survival outcome. We showed that mH2A1 is a new substrate of Skp2 SCF complex whose degradation by Skp2 promotes CDK8 gene and protein expression. Strikingly, breast tumour suppression on Skp2 deficiency can be rescued by mH2A1 knockdown or CDK8 restoration using mouse tumour models. We further show that CDK8 regulates p27 protein expression by facilitating Skp2-mediated p27 ubiquitination and degradation. Our study establishes a critical role of Skp2-mH2A1-CDK8 axis in breast cancer development and targeting this pathway offers a promising strategy for breast cancer therapy.
    Date: 2015-03-30
    Relation: Nature Communications. 2015 Mar 30;6:Article number 6641.
    Link to: http://dx.doi.org/10.1038/ncomms7641
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-1723&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000353040400001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?eid=2-s2.0-84926320663partnerID=40
    Appears in Collections:[Others] Periodical Articles

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