The Neglected Role of GSDMD C‐Terminal in Counteracting Type I Interferon Signaling
Source abstract
Abstract
Abstract The GSDMD N‐terminal fragment (GSDMD‐NT)‐mediated pyroptosis is extensively investigated. However, the role of the C‐terminal domain of GSDMD (GSDMD‐CT) is unexplored. This study demonstrates that GSDMD‐CT acts as a negative regulator that suppresses IFN‐I signaling during viral infection. Mechanistically, GSDMD‐CT, released upon virus infection, interacts separately with retinoic acid‐inducible gene I (RIG‐I) and tank‐binding kinase (TBK1), promoting the selective autophagic degradation of RIG‐I via K48‐linked polyubiquitination at Lys181 and TBK1 via K27‐linked polyubiquitination at Lys487 by the E3 ligase TRIM28, which serves as a recognition signal for the cargo receptor NDP52 and TOLLIP, respectively. Moreover, the P414, Q416, and E459 amino sites are crucial for GSDMD‐CT in counteracting antiviral responses. The findings highlight the role of GSDMD‐CT in inhibiting antiviral immunity, providing insights into how viruses manipulate host defense mechanisms to enhance infection.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: interferon and immune responses · Inflammasome and immune disorders · Ubiquitin and proteasome pathways
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
MOA Key Laboratory of Animal Virology Zhejiang University Center for Veterinary Sciences Zhejiang University Hangzhou 310058 China
Department of Veterinary Medicine College of Animal Sciences Zhejiang University Hangzhou 310058 China
College of Animal Science and Technology Guangxi University Nanning 530004 China
Key Laboratory of Applied Technology on Green‐Eco‐Healthy Animal Husbandry of Zhejiang Province College of Animal Science and Technology & College of Veterinary Medicine Zhejiang A&F University Hangzhou 311300 China
Zhejiang University‐Xinchang Joint Innovation Centre (TianMu Laboratory) Zhejiang University Shaoxing 312500 China
Funding
National Natural Science Foundation of China · National Key Research and Development Program of China
References (58)
Show source-provided references
1. 10.1016/j.tibs.2016.10.00410.1016/j.tibs.2016.10.004 ↗
2. 10.1038/nature1551410.1038/nature15514 ↗
3. 10.1038/s41392-021-00507-510.1038/s41392-021-00507-5 ↗
4. 10.1038/nature1554110.1038/nature15541 ↗
5. 10.1038/nature1368310.1038/nature13683 ↗
6. 10.1038/s41419-019-1413-810.1038/s41419-019-1413-8 ↗
7. 10.1073/pnas.160776911310.1073/pnas.1607769113 ↗
8. 10.1038/nature1859010.1038/nature18590 ↗
9. 10.1038/s41586-021-03478-310.1038/s41586-021-03478-3 ↗
10. Hu Y. · Proc. Natl. Acad. Sci. USA · 2022 · 119
11. 10.1016/j.molcel.2022.04.03310.1016/j.molcel.2022.04.033 ↗
12. 10.4049/jimmunol.160071410.4049/jimmunol.1600714 ↗
13. 10.1038/s41467-021-25015-610.1038/s41467-021-25015-6 ↗
14. 10.1038/ni.186110.1038/ni.1861 ↗
15. 10.1371/journal.ppat.100285710.1371/journal.ppat.1002857 ↗
16. 10.1016/j.celrep.2015.05.04710.1016/j.celrep.2015.05.047 ↗
17. 10.1371/journal.ppat.100612310.1371/journal.ppat.1006123 ↗
18. 10.1016/j.celrep.2024.11400410.1016/j.celrep.2024.114004 ↗
19. 10.1016/j.immuni.2018.07.00610.1016/j.immuni.2018.07.006 ↗
20. Zhao L. · mBio · 2021 · 13
21. 10.1038/s41467-024-47067-010.1038/s41467-024-47067-0 ↗
22. 10.1016/j.cub.2022.11.00210.1016/j.cub.2022.11.002 ↗
23. 10.1038/s41556-018-0037-z10.1038/s41556-018-0037-z ↗
24. 10.1016/j.tcb.2015.08.01010.1016/j.tcb.2015.08.010 ↗
25. 10.1038/s41580-022-00542-210.1038/s41580-022-00542-2 ↗
26. 10.1146/annurev-biochem-061516-04485910.1146/annurev-biochem-061516-044859 ↗
27. 10.1093/bib/bbab57410.1093/bib/bbab574 ↗
28. 10.1038/nature0573210.1038/nature05732 ↗
29. 10.1093/jmcb/mju00510.1093/jmcb/mju005 ↗
30. 10.1074/jbc.M112.36260810.1074/jbc.M112.362608 ↗
31. 10.1016/j.immuni.2017.02.01110.1016/j.immuni.2017.02.011 ↗
32. 10.1016/j.immuni.2014.01.01010.1016/j.immuni.2014.01.010 ↗
33. 10.1016/j.cell.2010.03.04010.1016/j.cell.2010.03.040 ↗
34. 10.1038/ni.223910.1038/ni.2239 ↗
35. 10.1016/j.tcb.2023.02.00710.1016/j.tcb.2023.02.007 ↗
36. 10.1016/j.molcel.2023.11.04010.1016/j.molcel.2023.11.040 ↗
37. Zhao T. · Trends Cell Biol. · 2025
38. 10.4049/jimmunol.180078810.4049/jimmunol.1800788 ↗
39. 10.1016/j.devcel.2022.09.01310.1016/j.devcel.2022.09.013 ↗
40. 10.1126/sciimmunol.abk209210.1126/sciimmunol.abk2092 ↗
41. 10.1016/j.cell.2023.05.02710.1016/j.cell.2023.05.027 ↗
42. 10.1038/s41590-022-01255-610.1038/s41590-022-01255-6 ↗
43. 10.1038/s41419-019-1579-010.1038/s41419-019-1579-0 ↗
44. Chen Z. · J. Virol. · 2024 · 99
45. 10.1126/science.aaf303610.1126/science.aaf3036 ↗
46. 10.1016/j.immuni.2017.11.01310.1016/j.immuni.2017.11.013 ↗
47. 10.1016/j.molcel.2017.09.00510.1016/j.molcel.2017.09.005 ↗
48. 10.15252/embj.20179678110.15252/embj.201796781 ↗
49. 10.1038/s41418-021-00833-910.1038/s41418-021-00833-9 ↗
50. 10.1126/sciadv.adg233910.1126/sciadv.adg2339 ↗
51. 10.1016/j.molcel.2016.08.02510.1016/j.molcel.2016.08.025 ↗
52. 10.1038/s41467-022-32957-y10.1038/s41467-022-32957-y ↗
53. 10.1038/nri.2016.5810.1038/nri.2016.58 ↗
54. 10.1093/bioinformatics/btp35210.1093/bioinformatics/btp352 ↗
55. 10.1038/s41587-019-0201-410.1038/s41587-019-0201-4 ↗
56. 10.1093/bioinformatics/btt65610.1093/bioinformatics/btt656 ↗
57. 10.1093/nar/gkab29410.1093/nar/gkab294 ↗
58. 10.1371/journal.pone.002465710.1371/journal.pone.0024657 ↗