Stat3 phosphorylation affects p53/p21 axis and KSHV lytic cycle activation

The Tyr705 STAT3 constitutive activation, besides promoting PEL cell survival, contributes to the maintenanceof viral latency. We found indeed that its de-phosphorylation by AG490 induced KSHV lytic cycle. Moreover,Tyr705 STAT3 de-phosphorylation, mediated by the activation of tyrosine phosphatases, together with the in-crease of Ser727 STAT3 phosphorylation contributed to KSHV lytic cycle induction by TPA. We then observedthat p53-p21 axis, essential for the induction of KSHV replication, was activated by the inhibition of Tyr705 andby the increase of Ser727 STAT3 phosphorylation. As a possible link between STAT3, p53-p21 and KSHV lyticcycle, we found that TPA and AG490 reduced the expression of KAP-1, promoting p53 stability, p21 tran-scription and KSHV lytic cycle activation in PEL cells