IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49045-y.html
   My bibliography  Save this article

The RNF214-TEAD-YAP signaling axis promotes hepatocellular carcinoma progression via TEAD ubiquitylation

Author

Listed:
  • Mengjia Lin

    (Zhejiang University
    Zhejiang University)

  • Xiaoyun Zheng

    (Zhejiang University
    Zhejiang University)

  • Jianing Yan

    (Zhejiang University School of Medicine)

  • Fei Huang

    (Zhejiang University)

  • Yilin Chen

    (Zhejiang University
    Zhejiang University)

  • Ran Ding

    (Zhejiang University
    Zhejiang University)

  • Jinkai Wan

    (Fudan University
    Fudan University)

  • Lei Zhang

    (Fudan University)

  • Chenliang Wang

    (Zhejiang University)

  • Jinchang Pan

    (Zhejiang University)

  • Xiaolei Cao

    (Zhejiang University
    Zhejiang University)

  • Kaiyi Fu

    (Zhejiang University)

  • Yan Lou

    (Zhejiang University)

  • Xin-Hua Feng

    (Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Junfang Ji

    (Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Bin Zhao

    (Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Fei Lan

    (Fudan University
    Fudan University)

  • Li Shen

    (Zhejiang University
    Zhejiang University)

  • Xianglei He

    (Zhejiang Provincial People’s Hospital)

  • Yunqing Qiu

    (Zhejiang University
    Zhejiang University)

  • Jianping Jin

    (Zhejiang University
    Zhejiang University
    Zhejiang University
    Zhejiang University)

Abstract

RNF214 is an understudied ubiquitin ligase with little knowledge of its biological functions or protein substrates. Here we show that the TEAD transcription factors in the Hippo pathway are substrates of RNF214. RNF214 induces non-proteolytic ubiquitylation at a conserved lysine residue of TEADs, enhances interactions between TEADs and YAP, and promotes transactivation of the downstream genes of the Hippo signaling. Moreover, YAP and TAZ could bind polyubiquitin chains, implying the underlying mechanisms by which RNF214 regulates the Hippo pathway. Furthermore, RNF214 is overexpressed in hepatocellular carcinoma (HCC) and inversely correlates with differentiation status and patient survival. Consistently, RNF214 promotes tumor cell proliferation, migration, and invasion, and HCC tumorigenesis in mice. Collectively, our data reveal RNF214 as a critical component in the Hippo pathway by forming a signaling axis of RNF214-TEAD-YAP and suggest that RNF214 is an oncogene of HCC and could be a potential drug target of HCC therapy.

Suggested Citation

  • Mengjia Lin & Xiaoyun Zheng & Jianing Yan & Fei Huang & Yilin Chen & Ran Ding & Jinkai Wan & Lei Zhang & Chenliang Wang & Jinchang Pan & Xiaolei Cao & Kaiyi Fu & Yan Lou & Xin-Hua Feng & Junfang Ji & , 2024. "The RNF214-TEAD-YAP signaling axis promotes hepatocellular carcinoma progression via TEAD ubiquitylation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49045-y
    DOI: 10.1038/s41467-024-49045-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49045-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-49045-y?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
    ---><---

    References listed on IDEAS

    as
    1. Min Sup Song & Leonardo Salmena & Arkaitz Carracedo & Ainara Egia & Francesco Lo-Coco & Julie Teruya-Feldstein & Pier Paolo Pandolfi, 2008. "The deubiquitinylation and localization of PTEN are regulated by a HAUSP–PML network," Nature, Nature, vol. 455(7214), pages 813-817, October.
    2. Luca Lignitto & Antonietta Arcella & Maria Sepe & Laura Rinaldi & Rossella Delle Donne & Adriana Gallo & Eduard Stefan & Verena A. Bachmann & Maria A. Oliva & Clelia Tiziana Storlazzi & Alberto L'Abba, 2013. "Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth," Nature Communications, Nature, vol. 4(1), pages 1-13, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Samira Schiefer & Benjamin G. Hale, 2024. "Proximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by PJA2," 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:15:y:2024:i:1:d:10.1038_s41467-024-49045-y. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.