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Karki R, Sundaram B, Sharma BR, et al. ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell Rep. 2021;37(3):109858doi: 10.1016/j.celrep.2021.109858.
Karki, R., Sundaram, B., Sharma, B. R., Lee, S., Malireddi, R. K. S., Nguyen, L. N., Christgen, S., Zheng, M., Wang, Y., Samir, P., Neale, G., Vogel, P., & Kanneganti, T. D. (2021). ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell reports, 37(3), 109858. https://doi.org/10.1016/j.celrep.2021.109858
Karki, Rajendra, et al. "ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis." Cell reports vol. 37,3 (2021): 109858. doi: https://doi.org/10.1016/j.celrep.2021.109858
Karki R, Sundaram B, Sharma BR, Lee S, Malireddi RKS, Nguyen LN, Christgen S, Zheng M, Wang Y, Samir P, Neale G, Vogel P, Kanneganti TD. ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell Rep. 2021 Oct 19;37(3):109858. doi: 10.1016/j.celrep.2021.109858. PMID: 34686350.
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Cell Rep. 2021 Oct 19;37(3):109858. doi: 10.1016/j.celrep.2021.109858.

ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis.

Cell reports

Rajendra Karki, Balamurugan Sundaram, Bhesh Raj Sharma, SangJoon Lee, R K Subbarao Malireddi, Lam Nhat Nguyen, Shelbi Christgen, Min Zheng, Yaqiu Wang, Parimal Samir, Geoffrey Neale, Peter Vogel, Thirumala-Devi Kanneganti

Affiliations

  1. Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  2. Hartwell Center for Bioinformatics & Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  3. Animal Resources Center and Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  4. Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: [email protected].

PMID: 34686350 DOI: 10.1016/j.celrep.2021.109858

Abstract

Cell death provides host defense and maintains homeostasis. Zα-containing molecules are essential for these processes. Z-DNA binding protein 1 (ZBP1) activates inflammatory cell death, PANoptosis, whereas adenosine deaminase acting on RNA 1 (ADAR1) serves as an RNA editor to maintain homeostasis. Here, we identify and characterize ADAR1's interaction with ZBP1, defining its role in cell death regulation and tumorigenesis. Combining interferons (IFNs) and nuclear export inhibitors (NEIs) activates ZBP1-dependent PANoptosis. ADAR1 suppresses this PANoptosis by interacting with the Zα2 domain of ZBP1 to limit ZBP1 and RIPK3 interactions. Adar1

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: ADAR1; IFN; PANoptosis; PANoptosome; ZBP1; apoptosis; inflammasome; necroptosis; pyroptosis; tumorigenesis

Conflict of interest statement

Declaration of interests St. Jude Children’s Research hospital filed a provisional patent application on the IFN and NEI treatment strategy described in this study, listing R.K. and T.-D.K. as invento

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