| Autor: |
Chaohui Lin, Edmund Osei Kuffour, Nina V. Fuchs, Christoph G.W. Gertzen, Jesko Kaiser, Maximilian Hirschenberger, Xiao Tang, Haifeng C. Xu, Oliver Michel, Ronny Tao, Alexandra Haase, Ulrich Martin, Thomas Kurz, Ingo Drexler, Boris Görg, Philipp A. Lang, Tom Luedde, Konstantin M.J. Sparrer, Holger Gohlke, Renate König, Carsten Münk |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 42, Iss 11, Pp 113277- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2023.113277 |
| Popis: |
Summary: Sensing of human immunodeficiency virus type 1 (HIV-1) DNA is mediated by the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling axis. Signal transduction and regulation of this cascade is achieved by post-translational modifications. Here we show that cGAS-STING-dependent HIV-1 sensing requires interferon-stimulated gene 15 (ISG15). ISG15 deficiency inhibits STING-dependent sensing of HIV-1 and STING agonist-induced antiviral response. Upon external stimuli, STING undergoes ISGylation at residues K224, K236, K289, K347, K338, and K370. Inhibition of STING ISGylation at K289 suppresses STING-mediated type Ⅰ interferon induction by inhibiting its oligomerization. Of note, removal of STING ISGylation alleviates gain-of-function phenotype in STING-associated vasculopathy with onset in infancy (SAVI). Molecular modeling suggests that ISGylation of K289 is an important regulator of oligomerization. Taken together, our data demonstrate that ISGylation at K289 is crucial for STING activation and represents an important regulatory step in DNA sensing of viruses and autoimmune responses. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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