IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-20107-1.html
   My bibliography  Save this article

TRIB3 promotes MYC-associated lymphoma development through suppression of UBE3B-mediated MYC degradation

Author

Listed:
  • Ke Li

    (Central South University
    Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Feng Wang

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Zhao-na Yang

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Ting-ting Zhang

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Yu-fen Yuan

    (Henan University of Science and Technology)

  • Chen-xi Zhao

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Zaiwuli Yeerjiang

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Bing Cui

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Fang Hua

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Xiao-xi Lv

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Xiao-wei Zhang

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Jiao-jiao Yu

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Shan-shan Liu

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Jin-mei Yu

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Shuang Shang

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Yang Xiao

    (Central South University)

  • Zhuo-wei Hu

    (Central South University
    Chinese Academy of Medical Sciences & Peking Union Medical College)

Abstract

The transcription factor MYC is deregulated in almost all human cancers, especially in aggressive lymphomas, through chromosomal translocation, amplification, and transcription hyperactivation. Here, we report that high expression of tribbles homologue 3 (TRIB3) positively correlates with elevated MYC expression in lymphoma specimens; TRIB3 deletion attenuates the initiation and progression of MYC-driven lymphoma by reducing MYC expression. Mechanistically, TRIB3 interacts with MYC to suppress E3 ubiquitin ligase UBE3B-mediated MYC ubiquitination and degradation, which enhances MYC transcriptional activity, causing high proliferation and self-renewal of lymphoma cells. Use of a peptide to disturb the TRIB3-MYC interaction together with doxorubicin reduces the tumor burden in MycEμ mice and patient-derived xenografts. The pathophysiological relevance of UBE3B, TRIB3 and MYC is further demonstrated in human lymphoma. Our study highlights a key mechanism for controlling MYC expression and a potential therapeutic option for treating lymphomas with high TRIB3-MYC expression.

Suggested Citation

  • Ke Li & Feng Wang & Zhao-na Yang & Ting-ting Zhang & Yu-fen Yuan & Chen-xi Zhao & Zaiwuli Yeerjiang & Bing Cui & Fang Hua & Xiao-xi Lv & Xiao-wei Zhang & Jiao-jiao Yu & Shan-shan Liu & Jin-mei Yu & Sh, 2020. "TRIB3 promotes MYC-associated lymphoma development through suppression of UBE3B-mediated MYC degradation," Nature Communications, Nature, vol. 11(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20107-1
    DOI: 10.1038/s41467-020-20107-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-20107-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-20107-1?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. Feng Wang & Yang Gao & Situ Xue & Luyao Zhao & Huimin Jiang & Tingting Zhang & Yunxuan Li & Chenxi Zhao & Fan Wu & Tana Siqin & Ying Liu & Jie Wu & Yechao Yan & Jian Yuan & Jian-dong Jiang & Ke Li, 2023. "SCARB2 drives hepatocellular carcinoma tumor initiating cells via enhanced MYC transcriptional activity," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Yejinpeng Wang & Lingao Ju & Gang Wang & Kaiyu Qian & Wan Jin & Mingxing Li & Jingtian Yu & Yiliang Shi & Yongzhi Wang & Yi Zhang & Yu Xiao & Xinghuan Wang, 2023. "DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC," Nature Communications, Nature, vol. 14(1), pages 1-17, 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:11:y:2020:i:1:d:10.1038_s41467-020-20107-1. 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.