Human cytomegalovirus IE86 protein aa 136–289 mediates STING degradation and blocks the cGAS-STING pathway
| Autor: | Bang Ju Park, Jun-Kyu Lee, Jung-Eun Kim, Yoon-Jae Song |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Human cytomegalovirus
Cytomegalovirus Applied Microbiology and Biotechnology Microbiology Immediate-Early Proteins Gene product Viral Proteins 03 medical and health sciences Transactivation medicine Humans Luciferase Receptor 030304 developmental biology chemistry.chemical_classification 0303 health sciences 030306 microbiology Chemistry Membrane Proteins General Medicine medicine.disease Nucleotidyltransferases Molecular biology eye diseases Amino acid Sting HEK293 Cells TRIF Cytomegalovirus Infections Trans-Activators Protein Binding |
| Zdroj: | Journal of Microbiology. 58:54-60 |
| ISSN: | 1976-3794 1225-8873 |
| Popis: | We previously reported that human cytomegalovirus (HCMV) 86 kDa immediate-early 2 gene product (IE86) promotes proteasome-dependent degradation of STING. In the present study, we determined the specific residues of IE86 responsible for STING degradation using a STING-firefly luciferase fusion protein expression system for quantitative meas-urement of STING protein levels. IE86 amino acids (aa) 136-289 were sufficient to promote STING degradation and further induced down-regulation of 2'3'-cyclic GMP-AMP (cGAMP)-mediated IFN-β promoter activation. Interestingly, transactivation domains (TAD) of the IE86 protein located at the N- and C-termini were required for down-regulation of Toll/interleukin-1 receptor (TIR) domain-containing adaptor-inducing interferon β (IFN-β) (TRIF)-mediated IFN-β-and p65/RelA-induced NF-κB-dependent promoter activation while amino acids (aa) 136-289 had no significant effects. Our collective data suggest that the IE86 protein utilizes the aa 136-289 region to promote STING degradation and inhibit the cGAS-STING pathway. |
| Databáze: | OpenAIRE |
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