STAT3 phosphorylation affects p53/p21 axis and KSHV lytic cycle activation
STAT3 phosphorylation affects p53/p21 axis and KSHV lytic cycle activation
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DOI：
10.1016/j.virol.2018.12.015
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发表时间：
2019-02-01
期刊：
影响因子：
3.7
通讯作者：
Cirone, Mara
中科院分区：
文献类型：
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作者：
Santarelli, Roberta;Carillo, Valentina;Cirone, Mara
Tyr705 STAT3组成型激活除了促进PEL细胞存活外，还有助于维持病毒潜伏期。我们发现AG490的去磷酸化确实诱导了KSHV抒情循环。此外，酪氨酸磷酸酶激活介导的Tyr705 STAT3去磷酸化和Ser727 STAT3磷酸化的增加共同促进了TPA诱导KSHV裂解循环。然后我们观察到p53-p21轴是诱导KSHV复制所必需的，通过抑制Tyr705和增加Ser727 STAT3磷酸化而被激活。作为STAT3、p53-p21与KSHV裂解周期之间可能的联系，我们发现TPA和AG490降低了KAP-1的表达，促进了p53的稳定性、p21的转录和KSHV裂解周期的激活。
The Tyr705 STAT3 constitutive activation, besides promoting PEL cell survival, contributes to the maintenance of viral latency. We found indeed that its de-phosphorylation by AG490 induced KSHV lyric cycle. Moreover, Tyr705 STAT3 de-phosphorylation, mediated by the activation of tyrosine phosphatases, together with the increase of Ser727 STAT3 phosphorylation contributed to KSHV lytic cycle induction by TPA. We then observed that p53-p21 axis, essential for the induction of KSHV replication, was activated by the inhibition of Tyr705 and by the increase of Ser727 STAT3 phosphorylation. As a possible link between STAT3, p53-p21 and KSHV lytic cycle, we found that TPA and AG490 reduced the expression of KAP-1, promoting p53 stability, p21 transcription and KSHV lytic cycle activation in PEL cells.