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

Virology. 2019 Feb:528:137-143. doi: 10.1016/j.virol.2018.12.015. Epub 2019 Jan 5.

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; STAT3; Ser727 STAT3; Tyr705 STAT3; p21; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Herpesvirus 8, Human / physiology*
  • Humans
  • Phosphorylation
  • STAT3 Transcription Factor / metabolism*
  • Staurosporine / pharmacology
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Suppressor Protein p53 / metabolism*
  • Virus Activation*

Substances

  • 12-O-tetradecanoylphorbol-1,3-acetate
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Staurosporine
  • Tetradecanoylphorbol Acetate