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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.

Citation

Sabina Sperandio, Corinne Barat, Miguel A Cabrita, Ana Gargaun, Maxim V Berezovski, Michel J Tremblay, Ian de Belle. TOE1 is an inhibitor of HIV-1 replication with cell-penetrating capability. Proceedings of the National Academy of Sciences of the United States of America. 2015 Jun 30;112(26):E3392-401

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PMID: 26056259

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