PMID:26056259

Citation	Sperandio, S, Barat, C, Cabrita, MA, Gargaun, A, Berezovski, MV, Tremblay, MJ and de Belle, I (2015) TOE1 is an inhibitor of HIV-1 replication with cell-penetrating capability. Proc. Natl. Acad. Sci. U.S.A. 112:E3392-401
Abstract	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.
Links	PubMed PMC4491801 Online version:10.1073/pnas.1500857112
Keywords	HEK293 Cells; HIV Long Terminal Repeat/genetics; HIV-1/genetics; HIV-1/physiology; HeLa Cells; Humans; Membrane Fusion/physiology; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; Protein Binding; Proteolysis; Transcriptional Activation; Virus Replication/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:TOE1		GO:0072495: host cell Cajal body	ECO:0000314:		C		FIGURE 4.B. Localization in HeLa cells 1 h after administration of recombinant EGFP-TOE1 fusion protein. Fusion protein involved a 6×His tag and were purified on a nickel column and administered to cultures of HeLa cells at a 1 μM concentration. CellMask Deep-Red plasma membrane stain was added immediately before live imaging at 0.25 μg/mL.	complete CACAO 12808
HUMAN:TOE1		GO:0015030: Cajal body	ECO:0000314:		C		FIGURE 4.B. Localization in HeLa cells 1 h after administration of recombinant EGFP-TOE1 fusion protein. Fusion protein involved a 6×His tag and were purified on a nickel column and administered to cultures of HeLa cells at a 1 μM concentration. CellMask Deep-Red plasma membrane stain was added immediately before live imaging at 0.25 μg/mL.	complete CACAO 12821

References

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