PARP14 Controls the Nuclear Accumulation of a Subset of Type I IFN-Inducible Proteins
PARP14 Controls the Nuclear Accumulation of a Subset of Type I IFN-Inducible Proteins
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DOI：
10.4049/jimmunol.1701117
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发表时间：
2018-04-01
影响因子：
4.4
通讯作者：
Natoli, Gioacchino
中科院分区：
文献类型：
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作者：
Caprara, Greta;Prosperini, Elena;Natoli, Gioacchino
聚adp核糖聚合酶（PARP）超家族的酶控制着许多相关的细胞过程，但对其在不同生理或疾病背景下的活性的精确理解在很大程度上是不完整的。我们发现，在内毒素激活小鼠巨噬细胞时，几个Parp基因的转录受到动态调节。PARP14被多种炎症刺激强烈诱导，并易位到受刺激的细胞核中。定量质谱分析表明，PARP14与一组ifn刺激基因（ISG）编码的蛋白结合，大多数具有未知的功能，并且是其核积累所必需的。此外，PARP14缺失减弱了IFN调控转录因子3调控的一级抗病毒反应基因的转录，包括Ifnb1，从而减少了IFN- β的产生和参与二级抗病毒反应的isg的激活。与上述数据一致，PARP14抑制鼠伤寒沙门菌在小鼠巨噬细胞中的增殖。总的来说，这些数据提示PARP14在抗菌反应控制中的作用，特别是在isg编码蛋白亚群的核活性中。
The enzymes of the poly-ADP-ribose polymerase (PARP) superfamily control many relevant cellular processes, but a precise understanding of their activities in different physiological or disease contexts is largely incomplete. We found that transcription of several Parp genes was dynamically regulated upon murine macrophage activation by endotoxin. PARP14 was strongly induced by several inflammatory stimuli and translocated into the nucleus of stimulated cells. Quantitative mass spectrometry analysis showed that PARP14 bound to a group of IFN-stimulated gene (ISG)-encoded proteins, most with an unknown function, and it was required for their nuclear accumulation. Moreover, PARP14 depletion attenuated transcription of primary antiviral response genes regulated by the IFN regulatory transcription factor 3, including Ifnb1, thus reducing IFN-beta production and activation of ISGs involved in the secondary antiviral response. In agreement with the above-mentioned data, PARP14 hindered Salmonella typhimurium proliferation in murine macrophages. Overall, these data hint at a role of PARP14 in the control of antimicrobial responses and specifically in nuclear activities of a subgroup of ISG-encoded proteins.