IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43945-1.html
   My bibliography  Save this article

Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC

Author

Listed:
  • Danfeng Dong

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Yuzhang Du

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Xuefeng Fei

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Hao Yang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Xiaofang Li

    (Northwest Women’s and Children’s Hospital)

  • Xiaobao Yang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Junrui Ma

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Shu Huang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Zhihui Ma

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Juanjuan Zheng

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • David W. Chan

    (The Chinese University of Hong Kong-Shenzhen)

  • Liyun Shi

    (Nanjing University of Chinese Medicine)

  • Yunqi Li

    (Shanghai Jiao Tong University School of Medicine)

  • Aaron T. Irving

    (Zhejiang University School of Medicine
    Zhejiang University)

  • Xiangliang Yuan

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Xiangfan Liu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Peihua Ni

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Yiqun Hu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Guangxun Meng

    (University of Chinese Academy of Sciences)

  • Yibing Peng

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Anthony Sadler

    (Hudson Institute of Medical Research
    Monash University)

  • Dakang Xu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

Abstract

Inflammasome activity is important for the immune response and is instrumental in numerous clinical conditions. Here we identify a mechanism that modulates the central Caspase-1 and NLR (Nod-like receptor) adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). We show that the function of ASC in assembling the inflammasome is controlled by its modification with SUMO (small ubiquitin-like modifier) and identify that the nuclear ZBTB16 (zinc-finger and BTB domain-containing protein 16) promotes this SUMOylation. The physiological significance of this activity is demonstrated through the reduction of acute inflammatory pathogenesis caused by a constitutive hyperactive inflammasome by ablating ZBTB16 in a mouse model of Muckle-Wells syndrome. Together our findings identify an further mechanism by which ZBTB16-dependent control of ASC SUMOylation assembles the inflammasome to promote this pro-inflammatory response.

Suggested Citation

  • Danfeng Dong & Yuzhang Du & Xuefeng Fei & Hao Yang & Xiaofang Li & Xiaobao Yang & Junrui Ma & Shu Huang & Zhihui Ma & Juanjuan Zheng & David W. Chan & Liyun Shi & Yunqi Li & Aaron T. Irving & Xianglia, 2023. "Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43945-1
    DOI: 10.1038/s41467-023-43945-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43945-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43945-1?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
    ---><---

    References listed on IDEAS

    as
    1. Yuan He & Melody Y. Zeng & Dahai Yang & Benny Motro & Gabriel Núñez, 2016. "NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux," Nature, Nature, vol. 530(7590), pages 354-357, February.
    2. Xiaomin Yao & Chenhong Zhang & Yue Xing & Guang Xue & Qianpeng Zhang & Fengwei Pan & Guojun Wu & Yingxin Hu & Qiuhong Guo & Ailing Lu & Xiaoming Zhang & Rongbin Zhou & Zhigang Tian & Benhua Zeng & Hon, 2017. "Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    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. Yening Zhang & Ling Luo & Xueming Xu & Jianfeng Wu & Fupeng Wang & Yanyan Lu & Ningjie Zhang & Yingying Ding & Ben Lu & Kai Zhao, 2023. "Acetylation is required for full activation of the NLRP3 inflammasome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Jakob Hartmann & Thomas Bajaj & Joy Otten & Claudia Klengel & Tim Ebert & Anne-Kathrin Gellner & Ellen Junglas & Kathrin Hafner & Elmira A. Anderzhanova & Fiona Tang & Galen Missig & Lindsay Rexrode &, 2024. "SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Kaiser Wani & Hind AlHarthi & Amani Alghamdi & Shaun Sabico & Nasser M. Al-Daghri, 2021. "Role of NLRP3 Inflammasome Activation in Obesity-Mediated Metabolic Disorders," IJERPH, MDPI, vol. 18(2), pages 1-21, January.
    4. Xiaodi Yu & Rosalie E. Matico & Robyn Miller & Dhruv Chauhan & Bertrand Schoubroeck & Karolien Grauwen & Javier Suarez & Beth Pietrak & Nandan Haloi & Yanting Yin & Gary John Tresadern & Laura Perez-B, 2024. "Structural basis for the oligomerization-facilitated NLRP3 activation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Tingting Niu & Charlotte Rosny & Séverine Chautard & Amaury Rey & Danish Patoli & Marine Groslambert & Camille Cosson & Brice Lagrange & Zhirong Zhang & Orane Visvikis & Sabine Hacot & Maggy Hologne &, 2021. "NLRP3 phosphorylation in its LRR domain critically regulates inflammasome assembly," Nature Communications, Nature, vol. 12(1), pages 1-15, 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:14:y:2023:i:1:d:10.1038_s41467-023-43945-1. 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.

    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.