IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-12001-2.html
   My bibliography  Save this article

CDK5-dependent phosphorylation and nuclear translocation of TRIM59 promotes macroH2A1 ubiquitination and tumorigenicity

Author

Listed:
  • Youzhou Sang

    (Shanghai Jiao Tong University)

  • Yanxin Li

    (Shanghai Jiao Tong University)

  • Yingwen Zhang

    (Shanghai Jiao Tong University)

  • Angel A. Alvarez

    (Northwestern University Feinberg School of Medicine)

  • Bo Yu

    (Shanghai Jiao Tong University)

  • Weiwei Zhang

    (Shanghai Jiao Tong University)

  • Bo Hu

    (Northwestern University Feinberg School of Medicine)

  • Shi-Yuan Cheng

    (Northwestern University Feinberg School of Medicine)

  • Haizhong Feng

    (Shanghai Jiao Tong University)

Abstract

Despite the development of adjuvant therapies, glioblastoma (GBM) patients remain incurable, thus justifying the urgent need of new therapies. CDK5 plays a critical role in GBM and is a potential target for GBM. However, the mechanism by which CDK5 promotes GBM tumorigenicity remains largely unknown. Here, we identify TRIM59 as a substrate of CDK5. EGFR-activated CDK5 directly binds to and phosphorylates TRIM59, a ubiquitin ligase at serine 308, which recruits PIN1 for cis–trans isomerization of TRIM59, leading to TRIM59 binding to importin α5 and nuclear translocation. Nuclear TRIM59 induces ubiquitination and degradation of the tumor suppressive histone variant macroH2A1, leading to enhanced STAT3 signaling activation and tumorigenicity. These findings are confirmed by inhibition of CDK5-activated TRIM59 activity that results in suppression of intracranial tumor growth. Correlative expressions of the components of this pathway are clinically prognostic. Our findings suggest targeting CDK5/TRIM59 signaling axis as a putative strategy for treating GBM.

Suggested Citation

  • Youzhou Sang & Yanxin Li & Yingwen Zhang & Angel A. Alvarez & Bo Yu & Weiwei Zhang & Bo Hu & Shi-Yuan Cheng & Haizhong Feng, 2019. "CDK5-dependent phosphorylation and nuclear translocation of TRIM59 promotes macroH2A1 ubiquitination and tumorigenicity," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12001-2
    DOI: 10.1038/s41467-019-12001-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-12001-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-12001-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Bo Yu & Jun Su & Qiqi Shi & Qing Liu & Jun Ma & Guoqing Ru & Lei Zhang & Jian Zhang & Xichun Hu & Jianming Tang, 2022. "KMT5A-methylated SNIP1 promotes triple-negative breast cancer metastasis by activating YAP signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Qiuhong Zhu & Panpan Liang & Hao Meng & Fangzhen Li & Wei Miao & Cuiying Chu & Wei Wang & Dongxue Li & Cong Chen & Yu Shi & Xingjiang Yu & Yifang Ping & Chaoshi Niu & Hai-bo Wu & Aili Zhang & Xiu-wu B, 2024. "Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12001-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.