SAMHD1's protein expression profile in humans
SAMHD1's protein expression profile in humans
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DOI：
10.1189/jlb.4hi0714-338rr
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发表时间：
2015-02
影响因子：
5.5
通讯作者：
Sarah Schmidt;Kristína Schenková;T. Adam;Elina Erikson;Judith Lehmann‐Koch;S. Sertel;B. Verhasselt;O. Fackler;F. Lasitschka;O. Keppler
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文献类型：
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作者：
Sarah Schmidt;Kristína Schenková;T. Adam;Elina Erikson;Judith Lehmann‐Koch;S. Sertel;B. Verhasselt;O. Fackler;F. Lasitschka;O. Keppler
脱氧核苷三磷酸三磷酸水解酶和3 ‘→5 ’外切酶SAMHD1限制体外非循环造血细胞中的HIV - 1感染，SAMHD1突变与AGS相关。目前对该细胞因子的体内表达和功能调控知之甚少。在这里，我们首先在来自bbbb210供体的25个人体组织和纯化的原代细胞群的微阵列上评估了SAMHD1蛋白的表达谱。在体内，SAMHD1在大多数造血来源的有核细胞中表达，包括组织驻留巨噬细胞、dc、pDCs、胸腺T细胞、单核细胞、NK细胞的所有发育阶段，以及B细胞中较低水平的表达。值得注意的是，SAMHD1在存在于肛门生殖器粘膜的HIV靶细胞中大量表达，为其作为可能影响HIV传播效率的细胞因子的评估提供了依据。接下来，我们研究了细胞激活状态和促炎细胞因子处理对SAMHD1表达和磷酸化的影响。激活的HIV易感CD4+ T细胞携带pSAMHD1(T592)，而静息的CD4+ T细胞和巨噬细胞表达具有HIV限制性活性的未磷酸化蛋白。令人惊讶的是，用IFN‐α、IFN‐γ、IL‐4、IL‐6、IL‐12、IL‐18、IL‐27或TNF‐α刺激这些原代细胞既不影响SAMHD1表达水平，也不影响苏氨酸592磷酸化。在活化的CD4+ T细胞中，只有IL‐1β适度下调SAMHD1。综上所述，本研究建立了SAMHD1在人体组织中的第一个横断面蛋白表达谱，并深入了解了其细胞周期依赖性磷酸化和对多种促炎细胞因子的无反应性。
The deoxynucleoside triphosphate triphosphohydrolase and 3′ → 5′ exonuclease SAMHD1 restricts HIV‐1 infection in noncycling hematopoietic cells in vitro, and SAMHD1 mutations are associated with AGS. Little is known about the in vivo expression and functional regulation of this cellular factor. Here, we first assessed the SAMHD1 protein expression profile on a microarray of 25 human tissues from >210 donors and in purified primary cell populations. In vivo, SAMHD1 was expressed in the majority of nucleated cells of hematopoietic origin, including tissue‐resident macrophages, DCs, pDCs, all developmental stages of thymic T cells, monocytes, NK cells, as well as at lower levels in B cells. Of note, SAMHD1 was abundantly expressed in HIV target cells residing in the anogenital mucosa, providing a basis for its evaluation as a cellular factor that may impact the efficiency of HIV transmission. Next, we examined the effect of the activation status and proinflammatory cytokine treatment of cells on expression and phosphorylation of SAMHD1. Activated, HIV‐susceptible CD4+ T cells carried pSAMHD1(T592), whereas resting CD4+ T cells and macrophages expressed the unphosphorylated protein with HIV‐restrictive activity. Surprisingly, stimulation of these primary cells with IFN‐α, IFN‐γ, IL‐4, IL‐6, IL‐12, IL‐18, IL‐27, or TNF‐α affected neither SAMHD1 expression levels nor threonine 592 phosphorylation. Only IL‐1β moderately down‐regulated SAMHD1 in activated CD4+ T cells. Taken together, this study establishes the first cross‐sectional protein expression profile of SAMHD1 in human tissues and provides insight into its cell cycle‐dependent phosphorylation and unresponsiveness to multiple proinflammatory cytokines.