TOE1是一种具有细胞穿透能力的HIV-1复制抑制剂。
TOE1 is an inhibitor of HIV-1 replication with cell-penetrating capability.
作者信息
Sperandio Sabina, Barat Corinne, Cabrita Miguel A, Gargaun Ana, Berezovski Maxim V, Tremblay Michel J, de Belle Ian
机构信息
Ottawa Hospital Research Institute, Program in Cancer Therapeutics, The Ottawa Hospital, Ottawa, ON, Canada K1H 8L6;
Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec, QC, Canada G1V 4G2;
出版信息
Proc Natl Acad Sci U S A. 2015 Jun 30;112(26):E3392-401. doi: 10.1073/pnas.1500857112. Epub 2015 Jun 8.
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.
Egr1的靶标（TOE1）是一种主要定位于核仁与卡哈尔体的核蛋白，它被鉴定为即刻早期基因Egr1的下游靶标。TOE1具有一个功能性去腺苷酸化结构域，并且已被证明参与剪接体组装。我们在此报告，TOE1可作为HIV-1复制的抑制剂发挥作用，并展示了支持TOE1与病毒特异性反式激活应答元件直接相互作用作为抑制机制一部分的证据。此外，我们表明TOE1可由活化的CD8(+) T淋巴细胞分泌，并且可被细胞毒性颗粒的主要成分之一丝氨酸蛋白酶颗粒酶B切割。全长和切割后的TOE1均可自发穿过质膜并穿透培养中的细胞，保留HIV-1抑制活性。已确定TOE1的抗病毒效力及其细胞穿透能力位于一个包含核定位序列的35个氨基酸区域内。
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