IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms14186.html
   My bibliography  Save this article

A critical role of DDRGK1 in endoplasmic reticulum homoeostasis via regulation of IRE1α stability

Author

Listed:
  • Jiang Liu

    (Institute of Aging Research, School of Medicine, Hangzhou Normal University)

  • Ying Wang

    (Institute of Aging Research, School of Medicine, Hangzhou Normal University)

  • Lizhi Song

    (Institute of Aging Research, School of Medicine, Hangzhou Normal University)

  • Linghua Zeng

    (Institute of Aging Research, School of Medicine, Hangzhou Normal University)

  • Weiwei Yi

    (Institute of Aging Research, School of Medicine, Hangzhou Normal University)

  • Ting Liu

    (Institute of Aging Research, School of Medicine, Hangzhou Normal University)

  • Huanzhen Chen

    (The First Hospital of Shanxi Medical University)

  • Miao Wang

    (Institute of Aging Research, School of Medicine, Hangzhou Normal University)

  • Zhenyu Ju

    (Institute of Aging Research, School of Medicine, Hangzhou Normal University)

  • Yu-Sheng Cong

    (Institute of Aging Research, School of Medicine, Hangzhou Normal University)

Abstract

Disturbance of endoplasmic reticulum (ER) homoeostasis induces ER stress and leads to activation of the unfolded protein response (UPR), which is an adaptive reaction that promotes cell survival or triggers apoptosis, when homoeostasis is not restored. DDRGK1 is an ER membrane protein and a critical component of the ubiquitin-fold modifier 1 (Ufm1) system. However, the functions and mechanisms of DDRGK1 in ER homoeostasis are largely unknown. Here, we show that depletion of DDRGK1 induces ER stress and enhances ER stress-induced apoptosis in both cancer cells and hematopoietic stem cells (HSCs). Depletion of DDRGK1 represses IRE1α-XBP1 signalling and activates the PERK-eIF2α-CHOP apoptotic pathway by targeting the ER-stress sensor IRE1α. We further demonstrate that DDRGK1 regulates IRE1α protein stability via its interaction with the kinase domain of IRE1α, which is dependent on its ufmylation modification. Altogether, our results provide evidence that DDRGK1 is essential for ER homoeostasis regulation.

Suggested Citation

  • Jiang Liu & Ying Wang & Lizhi Song & Linghua Zeng & Weiwei Yi & Ting Liu & Huanzhen Chen & Miao Wang & Zhenyu Ju & Yu-Sheng Cong, 2017. "A critical role of DDRGK1 in endoplasmic reticulum homoeostasis via regulation of IRE1α stability," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14186
    DOI: 10.1038/ncomms14186
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms14186
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms14186?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
    ---><---

    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:8:y:2017:i:1:d:10.1038_ncomms14186. 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.