TOE1 is an inhibitor of HIV-1 replication with cell-penetrating capability
| Autor: | Michel J. Tremblay, Ana Gargaun, Ian de Belle, Miguel A. Cabrita, Maxim V. Berezovski, Corinne Barat, Sabina Sperandio |
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| Rok vydání: | 2015 |
| Předmět: |
Transcriptional Activation
Nucleolus Biology Virus Replication Membrane Fusion Commentaries Humans Nuclear protein HIV Long Terminal Repeat Multidisciplinary Nuclear Proteins Molecular biology Cell biology Granzyme B HEK293 Cells PNAS Plus Viral replication Cajal body Granzyme Proteolysis HIV-1 biology.protein Immediate early gene Nuclear localization sequence HeLa Cells Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences. 112 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Target of Egr1 (TOE1) is a nuclear protein localized primarily in nucleoli and Cajal bodies that was identified as a downstream target of the immediate early gene Egr1. TOE1 displays a functional deadenylation domain and has been shown to participate in spliceosome assembly. We report here that TOE1 can function as an inhibitor of HIV-1 replication and show evidence that supports a direct interaction of TOE1 with the viral specific transactivator response element as part of the inhibitory mechanism. In addition, we show that TOE1 can be secreted by activated CD8(+) T lymphocytes and can be cleaved by the serine protease granzyme B, one of the main components of cytotoxic granules. Both full-length and cleaved TOE1 can spontaneously cross the plasma membrane and penetrate cells in culture, retaining HIV-1 inhibitory activity. Antiviral potency of TOE1 and its cell-penetrating capability have been identified to lie within a 35-amino-acid region containing the nuclear localization sequence. |
| Databáze: | OpenAIRE |
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