STAT3 phosphorylation affects p53/p21 axis and KSHV lytic cycle activation

Roberta Santarelli; Valentina Carillo; Maria Anele Romeo; Aurelia Gaeta; Cristina Nazzari; Roberta Gonnella; Marisa Granato; Gabriella D'Orazi; Alberto Faggioni; Mara Cirone

doi:10.1016/j.virol.2018.12.015

STAT3 phosphorylation affects p53/p21 axis and KSHV lytic cycle activation

Roberta Santarelli, Valentina Carillo, Maria Anele Romeo, Aurelia Gaeta, Cristina Nazzari, Roberta Gonnella, Marisa Granato, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone

Istituto Regina Elena

Research output: Contribution to journal › Article

Abstract

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 lytic 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.

Original language	English
Pages (from-to)	137-143
Number of pages	7
Journal	Virology
Volume	528
DOIs	https://doi.org/10.1016/j.virol.2018.12.015
Publication status	Published - Feb 2019

Keywords

KAP-1
KSHV
Lytic cycle
p21
p53
Ser727 STAT3
STAT3
Tyr705 STAT3

ASJC Scopus subject areas

Virology

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title = "STAT3 phosphorylation affects p53/p21 axis and KSHV lytic cycle activation",

abstract = "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 lytic 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.",

keywords = "KAP-1, KSHV, Lytic cycle, p21, p53, Ser727 STAT3, STAT3, Tyr705 STAT3",

author = "Roberta Santarelli and Valentina Carillo and Romeo, {Maria Anele} and Aurelia Gaeta and Cristina Nazzari and Roberta Gonnella and Marisa Granato and Gabriella D'Orazi and Alberto Faggioni and Mara Cirone",

year = "2019",

month = feb,

doi = "10.1016/j.virol.2018.12.015",

language = "English",

volume = "528",

pages = "137--143",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press Inc.",

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T1 - STAT3 phosphorylation affects p53/p21 axis and KSHV lytic cycle activation

AU - Santarelli, Roberta

AU - Carillo, Valentina

AU - Romeo, Maria Anele

AU - Gaeta, Aurelia

AU - Nazzari, Cristina

AU - Gonnella, Roberta

AU - Granato, Marisa

AU - D'Orazi, Gabriella

AU - Faggioni, Alberto

AU - Cirone, Mara

PY - 2019/2

Y1 - 2019/2

N2 - 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 lytic 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.

AB - 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 lytic 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.

KW - KAP-1

KW - KSHV

KW - Lytic cycle

KW - p21

KW - p53

KW - Ser727 STAT3

KW - STAT3

KW - Tyr705 STAT3

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DO - 10.1016/j.virol.2018.12.015

M3 - Article

C2 - 30616203

AN - SCOPUS:85060047040

VL - 528

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JO - Virology

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