IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-56336-5.html
   My bibliography  Save this article

Chemical tools to define and manipulate interferon-inducible Ubl protease USP18

Author

Listed:
  • Griffin J. Davis

    (National Cancer Institute, National Institutes of Health)

  • Anthony O. Omole

    (National Cancer Institute, National Institutes of Health)

  • Yejin Jung

    (National Cancer Institute, National Institutes of Health)

  • Wioletta Rut

    (Wroclaw University of Science and Technology)

  • Ronald Holewinski

    (Frederick National Laboratory for Cancer Research, Leidos Biomedical Research)

  • Kiall F. Suazo

    (Frederick National Laboratory for Cancer Research, Leidos Biomedical Research)

  • Hong-Rae Kim

    (National Cancer Institute, National Institutes of Health
    Korea University)

  • Mo Yang

    (National Cancer Institute, National Institutes of Health)

  • Thorkell Andresson

    (Frederick National Laboratory for Cancer Research, Leidos Biomedical Research)

  • Marcin Drag

    (Wroclaw University of Science and Technology)

  • Euna Yoo

    (National Cancer Institute, National Institutes of Health)

Abstract

Ubiquitin-specific protease 18 (USP18) is a multifunctional cysteine protease primarily responsible for deconjugating the interferon-inducible ubiquitin-like modifier ISG15 from protein substrates. Here, we report the design and synthesis of activity-based probes (ABPs) that incorporate unnatural amino acids into the C-terminal tail of ISG15, enabling the selective detection of USP18 activity over other ISG15 cross-reactive deubiquitinases (DUBs) such as USP5 and USP14. Combined with a ubiquitin-based DUB ABP, the USP18 ABP is employed in a chemoproteomics screening platform to identify and assess inhibitors of DUBs including USP18. We further demonstrate that USP18 ABPs can be utilized to profile differential activities of USP18 in lung cancer cell lines, providing a strategy that will help define the activity-related landscape of USP18 in different disease states and unravel important (de)ISGylation-dependent biological processes.

Suggested Citation

  • Griffin J. Davis & Anthony O. Omole & Yejin Jung & Wioletta Rut & Ronald Holewinski & Kiall F. Suazo & Hong-Rae Kim & Mo Yang & Thorkell Andresson & Marcin Drag & Euna Yoo, 2025. "Chemical tools to define and manipulate interferon-inducible Ubl protease USP18," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56336-5
    DOI: 10.1038/s41467-025-56336-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-56336-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-56336-5?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. Wai Cheung Chan & Xiaoxi Liu & Robert S. Magin & Nicholas M. Girardi & Scott B. Ficarro & Wanyi Hu & Maria I. Tarazona Guzman & Cara A. Starnbach & Alejandra Felix & Guillaume Adelmant & Anthony C. Va, 2023. "Accelerating inhibitor discovery for deubiquitinating enzymes," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Kei-ichiro Arimoto & Sayuri Miyauchi & Ty D. Troutman & Yue Zhang & Mengdan Liu & Samuel A. Stoner & Amanda G. Davis & Jun-Bao Fan & Yi-Jou Huang & Ming Yan & Christopher K. Glass & Dong-Er Zhang, 2023. "Expansion of interferon inducible gene pool via USP18 inhibition promotes cancer cell pyroptosis," Nature Communications, Nature, vol. 14(1), pages 1-22, 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. George S. Biggs & Emma E. Cawood & Aini Vuorinen & William J. McCarthy & Harry Wilders & Ioannis G. Riziotis & Antonie J. Zouwen & Jonathan Pettinger & Luke Nightingale & Peiling Chen & Andrew J. Powe, 2025. "Robust proteome profiling of cysteine-reactive fragments using label-free chemoproteomics," Nature Communications, Nature, vol. 16(1), pages 1-14, 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:16:y:2025:i:1:d:10.1038_s41467-025-56336-5. 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.