APE1/Ref-1 regulates PTEN expression mediated by Egr-1

Damiano Fantini, Carlo Vascotto, Marta Deganuto, Nicoletta Bivi, Stefano Gustincich, Gabriella Marcon, Franco Quadrifoglio, Giuseppe Damante, Kishor K. Bhakat, Sankar Mitra, Gianluca Tell

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

APE1/Ref-1, the mammalian ortholog of E. coli Xth, and a multifunctional protein possessing both DNA repair and transcriptional regulatory activities, has dual role in controlling cellular response to oxidative stress. It is rate-limiting in repair of oxidative DNA damage including strand breaks and also has co-transcriptional activity by modulating genes expression directly regulated by Egr-1 and p53 transcription factors. PTEN, a phosphoinositide phosphatase, acts as an 'off' switch in the PI-3 kinase/Akt signalling pathway and regulates cell growth and survival. It is shown here that transient alteration in the APE1 level in HeLa cells modulates PTEN expression and that acetylatable APE1 is required for the activation of the PTEN gene. Acetylation of APE1 enhances its binding to distinct trans-acting complexes involved in activation or repression. The acetylated protein is deacetylated in vivo by histone deacetylases. It was found that exposure of HeLa cells to H2O2 and to histone deacetylase inhibitors increases acetylation of APE1 and induction of PTEN. The absence of such induction in APE1-downregulated HeLa cells confirmed APE1's role in regulating inducible PTEN expression. That APE1-dependent PTEN expression is mediated by Egr-1 was supported by experiments with cells ectopically expressing Egr-1. Thus, the data open new perspectives in the comprehension of the many functions exerted by APE1 in controlling cell response to oxidative stress.

Original languageEnglish (US)
Pages (from-to)20-29
Number of pages10
JournalFree Radical Research
Volume42
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • APE1/Ref-1
  • Egr-1
  • Histone acetyltransferase inhibitors
  • Oxidative stress response
  • PTEN
  • siRNA

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'APE1/Ref-1 regulates PTEN expression mediated by Egr-1'. Together they form a unique fingerprint.

  • Cite this

    Fantini, D., Vascotto, C., Deganuto, M., Bivi, N., Gustincich, S., Marcon, G., Quadrifoglio, F., Damante, G., Bhakat, K. K., Mitra, S., & Tell, G. (2008). APE1/Ref-1 regulates PTEN expression mediated by Egr-1. Free Radical Research, 42(1), 20-29. https://doi.org/10.1080/10715760701765616