Ricerc@Sapienza

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.

The unfolded protein response (UPR) is an adaptive response to intrinsic and external stressors, and it is mainly activated by the accumulation of misfolded proteins at the endoplasmic reticulum (ER) lumen producing ER stress. The UPR signaling network is interconnected with autophagy, the proteolytic machinery specifically devoted to clearing misfolded proteins in order to survive bioenergetic stress and/or induce cell death.