Genome-Wide analysis and proteomic studies reveal APE1/Ref-1 multifunctional role in mammalian cells

Carlo Vascotto, Laura Cesaratto, Leo A H Zeef, Marta Deganuto, Chiara Dambrosio, Andrea Scaloni, Milena Romanello, Giuseppe Damante, Giulio Taglialatela, Daniela Delneri, Mark R. Kelley, Sankar Mitra, Franco Quadrifoglio, Gianluca Tell

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Apurinic apyrimidinic endonuclease/redox effector factor 1 (APE1/Ref-1) protects cells from oxidative stress by acting as a central enzyme in base excision repair pathways of DNA lesions and through its independent activity as a redox transcriptional co-activator. Dysregulation of this protein has been associated with cancer development. At present, contrasting data have been published regarding the biological relevance of the two functions as well as the molecular mechanisms involved. Here, we combined both mRNA expression profiling and prote- omic analysis to determine the molecular changes associated with APE1 loss-of-expression induced by siRNA technology. This approach identified a role of APE1 in cell growth, apop- tosis, intracellular redox state, mitochondrial function, and cytoskeletal structure. Overall, our data show that APE1 acts as a hub in coordinating different and vital functions in mammalian cells, highlighting the molecular determinants of the multifunctional nature of APE1 protein.

Original languageEnglish (US)
Pages (from-to)1058-1074
Number of pages17
JournalProteomics
Volume9
Issue number4
DOIs
StatePublished - Feb 2009

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Keywords

  • APE1
  • Apoptosis
  • Oxidative stress
  • Ref-1
  • SiRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Vascotto, C., Cesaratto, L., Zeef, L. A. H., Deganuto, M., Dambrosio, C., Scaloni, A., Romanello, M., Damante, G., Taglialatela, G., Delneri, D., Kelley, M. R., Mitra, S., Quadrifoglio, F., & Tell, G. (2009). Genome-Wide analysis and proteomic studies reveal APE1/Ref-1 multifunctional role in mammalian cells. Proteomics, 9(4), 1058-1074. https://doi.org/10.1002/pmic.200800638