Regulation of Interferon Induction by the Ubiquitin-Like Modifier FAT10
The revelation that the human major histocompatibility complex (MHC) class I locus encodes a ubiquitin-like protein designated HLA-F adjacent transcript 10 (FAT10) or ubiquitin D (UBD) has attracted increasing attention to the function of this protein. Interestingly, the pro-inflammatory cytokines i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/6/951 |
| _version_ | 1797564344818466816 |
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| author | Mei Min Mah Nicola Roverato Marcus Groettrup |
| author_facet | Mei Min Mah Nicola Roverato Marcus Groettrup |
| author_sort | Mei Min Mah |
| collection | DOAJ |
| description | The revelation that the human major histocompatibility complex (MHC) class I locus encodes a ubiquitin-like protein designated HLA-F adjacent transcript 10 (FAT10) or ubiquitin D (UBD) has attracted increasing attention to the function of this protein. Interestingly, the pro-inflammatory cytokines interferon (IFN)-γ and tumor necrosis factor (TNF) α synergize to strongly induce FAT10 expression, thereby suggesting a role of FAT10 in the immune response. Recent reports that FAT10 downregulates type I interferon production while it upregulates IFN-γ pose mechanistic questions on how FAT10 differentially regulates interferon induction. Several covalent and non-covalent binding partners of FAT10 involved in signal transduction pathways leading to IFN synthesis have been identified. After introducing FAT10, we review here recent insights into how FAT10 affects proteins in the interferon pathways, like the virus-responsive pattern recognition receptor RIG-I, the ubiquitin ligase ZNF598, and the deubiquitylating enzyme OTUB1. Moreover, we outline the consequences of FAT10 deficiency on interferon synthesis and viral expansion in mice and human cells. We discuss the need for covalent isopeptide linkage of FAT10 to the involved target proteins and the concomitant targeting for proteasomal degradation. After years of investigating the elusive biological functions of this fascinating ubiquitin-like modifier, we review the emerging evidence for a novel role of FAT10 in interferon regulation. |
| first_indexed | 2024-03-10T18:56:00Z |
| format | Article |
| id | doaj.art-17798558153c44ca9c8ff9d735f6a367 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T18:56:00Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-17798558153c44ca9c8ff9d735f6a3672023-11-20T04:45:05ZengMDPI AGBiomolecules2218-273X2020-06-0110695110.3390/biom10060951Regulation of Interferon Induction by the Ubiquitin-Like Modifier FAT10Mei Min Mah0Nicola Roverato1Marcus Groettrup2Division of Immunology, Department of Biology, University of Konstanz, 78457 Konstanz, GermanyDivision of Immunology, Department of Biology, University of Konstanz, 78457 Konstanz, GermanyDivision of Immunology, Department of Biology, University of Konstanz, 78457 Konstanz, GermanyThe revelation that the human major histocompatibility complex (MHC) class I locus encodes a ubiquitin-like protein designated HLA-F adjacent transcript 10 (FAT10) or ubiquitin D (UBD) has attracted increasing attention to the function of this protein. Interestingly, the pro-inflammatory cytokines interferon (IFN)-γ and tumor necrosis factor (TNF) α synergize to strongly induce FAT10 expression, thereby suggesting a role of FAT10 in the immune response. Recent reports that FAT10 downregulates type I interferon production while it upregulates IFN-γ pose mechanistic questions on how FAT10 differentially regulates interferon induction. Several covalent and non-covalent binding partners of FAT10 involved in signal transduction pathways leading to IFN synthesis have been identified. After introducing FAT10, we review here recent insights into how FAT10 affects proteins in the interferon pathways, like the virus-responsive pattern recognition receptor RIG-I, the ubiquitin ligase ZNF598, and the deubiquitylating enzyme OTUB1. Moreover, we outline the consequences of FAT10 deficiency on interferon synthesis and viral expansion in mice and human cells. We discuss the need for covalent isopeptide linkage of FAT10 to the involved target proteins and the concomitant targeting for proteasomal degradation. After years of investigating the elusive biological functions of this fascinating ubiquitin-like modifier, we review the emerging evidence for a novel role of FAT10 in interferon regulation.https://www.mdpi.com/2218-273X/10/6/951interferonubiquitinFAT10signal transductionRIG-Iinfluenza virus |
| spellingShingle | Mei Min Mah Nicola Roverato Marcus Groettrup Regulation of Interferon Induction by the Ubiquitin-Like Modifier FAT10 Biomolecules interferon ubiquitin FAT10 signal transduction RIG-I influenza virus |
| title | Regulation of Interferon Induction by the Ubiquitin-Like Modifier FAT10 |
| title_full | Regulation of Interferon Induction by the Ubiquitin-Like Modifier FAT10 |
| title_fullStr | Regulation of Interferon Induction by the Ubiquitin-Like Modifier FAT10 |
| title_full_unstemmed | Regulation of Interferon Induction by the Ubiquitin-Like Modifier FAT10 |
| title_short | Regulation of Interferon Induction by the Ubiquitin-Like Modifier FAT10 |
| title_sort | regulation of interferon induction by the ubiquitin like modifier fat10 |
| topic | interferon ubiquitin FAT10 signal transduction RIG-I influenza virus |
| url | https://www.mdpi.com/2218-273X/10/6/951 |
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