IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v4y2013i1d10.1038_ncomms3562.html
   My bibliography  Save this article

Smad6 inhibits non-canonical TGF-β1 signalling by recruiting the deubiquitinase A20 to TRAF6

Author

Listed:
  • Su Myung Jung

    (Sungkyunkwan University)

  • Ji-Hyung Lee

    (Sungkyunkwan University)

  • Jinyoung Park

    (Sungkyunkwan University School of Medicine
    Korea University)

  • Young Sun Oh

    (Sungkyunkwan University
    Medical Bioconvergence Research Center, Seoul National University)

  • Sung Kyun Lee

    (Sungkyunkwan University)

  • Jin Seok Park

    (Sungkyunkwan University)

  • Youn Sook Lee

    (Sungkyunkwan University)

  • Jun Hwan Kim

    (Sungkyunkwan University)

  • Jae Young Lee

    (Sungkyunkwan University)

  • Yoe-Sik Bae

    (Sungkyunkwan University)

  • Seung-Hoi Koo

    (Korea University)

  • Seong-Jin Kim

    (CHA Cancer Institute, CHA University)

  • Seok Hee Park

    (Sungkyunkwan University)

Abstract

Transforming growth factor (TGF)-β, a pivotal cytokine involved in a variety of cellular functions, transmits signals through Smad-dependent canonical and Smad-independent noncanonical pathways. In contrast to the canonical TGF-β pathway, it is unknown how noncanonical TGF-β pathways are negatively regulated. Here we demonstrate that the inhibitory Smad Smad6, but not Smad7, negatively regulates TGF-β1-induced activation of the TRAF6-TAK1-p38 MAPK/JNK pathway, a noncanonical TGF-β pathway. TGF-β1-induced Smad6 abolishes K63-linked polyubiquitination of TRAF6 by recruiting the A20 deubiquitinating enzyme in AML-12 mouse liver cells and primary hepatocytes. In addition, the knockdown of Smad6 or A20 in an animal model or cell culture system maintains TAK1 and p38 MAPK/JNK phosphorylation and increases apoptosis, emphasizing the crucial role of the Smad6-A20 axis in negative regulation of the TGF-β1-TRAF6-TAK1-p38 MAPK/JNK pathway. Therefore, our findings provide insight into the molecular mechanisms underlying negative regulation of noncanonical TGF-β pathways.

Suggested Citation

  • Su Myung Jung & Ji-Hyung Lee & Jinyoung Park & Young Sun Oh & Sung Kyun Lee & Jin Seok Park & Youn Sook Lee & Jun Hwan Kim & Jae Young Lee & Yoe-Sik Bae & Seung-Hoi Koo & Seong-Jin Kim & Seok Hee Park, 2013. "Smad6 inhibits non-canonical TGF-β1 signalling by recruiting the deubiquitinase A20 to TRAF6," Nature Communications, Nature, vol. 4(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3562
    DOI: 10.1038/ncomms3562
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms3562
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms3562?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. Mangalakumari Jeyanathan & Sam Afkhami & Michael R. D’Agostino & Imran Satia & Dominik K. Fritz & Kate Miyasaki & Jann C. Ang & Anna Zganiacz & Karen J. Howie & Marilyn Swinton & Emilio Aguirre & Mich, 2025. "Induction of lung mucosal immunity by a next-generation inhaled aerosol COVID-19 vaccine: an open-label, multi-arm phase 1 clinical trial," Nature Communications, Nature, vol. 16(1), pages 1-21, 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:4:y:2013:i:1:d:10.1038_ncomms3562. 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.