論文 - 詳細
| RRC ID | 58662 |
|---|---|
| 著者 | Muscolino E, Schmitz R, Loroch S, Caragliano E, Schneider C, Rizzato M, Kim YH, Krause E, Juranić Lisnić V, Sickmann A, Reimer R, Ostermann E, Brune W. |
| タイトル | Herpesviruses induce aggregation and selective autophagy of host signalling proteins NEMO and RIPK1 as an immune-evasion mechanism. |
| ジャーナル | Nat Microbiol |
| Abstract |
Viruses manipulate cellular signalling by inducing the degradation of crucial signal transducers, usually via the ubiquitin-proteasome pathway. Here, we show that the murine cytomegalovirus (Murid herpesvirus 1) M45 protein induces the degradation of two cellular signalling proteins, the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) essential modulator (NEMO) and the receptor-interacting protein kinase 1 (RIPK1), via a different mechanism: it induces their sequestration as insoluble protein aggregates and subsequently facilitates their degradation by autophagy. Aggregation of target proteins requires a distinct sequence motif in M45, which we termed 'induced protein aggregation motif'. In a second step, M45 recruits the retromer component vacuolar protein sorting 26B (VPS26B) and the microtubule-associated protein light chain 3 (LC3)-interacting adaptor protein TBC1D5 to facilitate degradation of aggregates by selective autophagy. The induced protein aggregation motif is conserved in M45-homologous proteins of several human herpesviruses, including herpes simplex virus, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, but is only partially conserved in the human cytomegalovirus UL45 protein. We further show that the HSV-1 ICP6 protein induces RIPK1 aggregation and degradation in a similar fashion to M45. These data suggest that induced protein aggregation combined with selective autophagy of aggregates (aggrephagy) represents a conserved viral immune-evasion mechanism. |
| 巻・号 | 5(2) |
| ページ | 331-342 |
| 公開日 | 2020-2-1 |
| DOI | 10.1038/s41564-019-0624-1 |
| PII | 10.1038/s41564-019-0624-1 |
| PMID | 31844296 |
| MeSH | Animals Autophagy / immunology Autophagy-Related Protein 5 / deficiency Autophagy-Related Protein 5 / genetics Cells, Cultured HEK293 Cells Herpesviridae / immunology* Herpesviridae / metabolism Herpesviridae / pathogenicity Herpesvirus 1, Human / immunology Herpesvirus 1, Human / metabolism Herpesvirus 1, Human / pathogenicity Host Microbial Interactions / immunology Humans Immune Evasion Intracellular Signaling Peptides and Proteins / chemistry Intracellular Signaling Peptides and Proteins / immunology* Intracellular Signaling Peptides and Proteins / metabolism Mice Mice, Inbred C57BL Models, Biological Muromegalovirus / immunology Muromegalovirus / metabolism Muromegalovirus / pathogenicity Protein Aggregates / immunology Proteolysis Receptor-Interacting Protein Serine-Threonine Kinases / chemistry Receptor-Interacting Protein Serine-Threonine Kinases / immunology* Receptor-Interacting Protein Serine-Threonine Kinases / metabolism Ribonucleotide Reductases / genetics Ribonucleotide Reductases / immunology Ribonucleotide Reductases / metabolism Viral Proteins / genetics Viral Proteins / immunology Viral Proteins / metabolism |
| IF | 15.54 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 14 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Atg5^(-/-)MEF(RCB2711) |