The tumor suppressor PTEN has a critical role in antiviral innate immunity
The tumor suppressor PTEN has a critical role in antiviral innate immunity
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肿瘤抑制因子 PTEN 在抗病毒先天免疫中发挥着关键作用
DOI：
10.1038/ni.3311
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发表时间：
2016-03-01
影响因子：
30.5
通讯作者：
Guo, Deyin
中科院分区：
文献类型：
--
作者：
Li, Shun;Zhu, Mingzhu;Guo, Deyin
编码PTEN的基因是人类癌症中最常突变的肿瘤抑制基因之一。虽然PTEN在肿瘤抑制中的功能已经得到很好的确立，但其与抗微生物免疫的关系仍然未知。在此，我们发现了PTEN在诱导I型干扰素中的关键作用，I型干扰素是抗病毒先天免疫的标志，其独立于激酶PI（3）K和Akt的途径。PTEN控制IRF 3（一种负责IFN-β产生的主转录因子）进入细胞核。我们进一步确定了IRF 3的Ser 97处的PTEN控制的负磷酸化位点，并发现通过PTEN的磷酸酶活性从这种负调节中释放对于IRF 3的激活及其进入细胞核是必不可少的。我们的研究确定了肿瘤抑制和先天免疫中PTEN和IRF 3之间的串扰。
The gene encoding PTEN is one of the most frequently mutated tumor suppressor-encoding genes in human cancer. While PTEN's function in tumor suppression is well established, its relationship to anti-microbial immunity remains unknown. Here we found a pivotal role for PTEN in the induction of type I interferon, the hallmark of antiviral innate immunity, that was independent of the pathway of the kinases PI(3)K and Akt. PTEN controlled the import of IRF3, a master transcription factor responsible for IFN-beta production, into the nucleus. We further identified a PTEN-controlled negative phosphorylation site at Ser97 of IRF3 and found that release from this negative regulation via the phosphatase activity of PTEN was essential for the activation of IRF3 and its import into the nucleus. Our study identifies crosstalk between PTEN and IRF3 in tumor suppression and innate immunity.