title: Genome-wide analysis and proteomic studies reveal APE1/Ref-1 multifunctional role in mammalian cells.
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 proteomic 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, apoptosis, 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.
authors.affiliation: Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Vascotto
authors.forename: Laura
authors.initials: L
authors.lastname: Cesaratto
authors.forename: Leo A H
authors.initials: LA
authors.lastname: Zeef
authors.forename: Marta
authors.initials: M
authors.lastname: Deganuto
authors.forename: Chiara
authors.initials: C
authors.lastname: D'Ambrosio
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.forename: Milena
authors.initials: M
authors.lastname: Romanello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
authors.forename: Giulio
authors.initials: G
authors.lastname: Taglialatela
authors.forename: Daniela
authors.initials: D
authors.lastname: Delneri
authors.forename: Mark R
authors.initials: MR
authors.lastname: Kelley
authors.forename: Sankar
authors.initials: S
authors.lastname: Mitra
authors.forename: Franco
authors.initials: F
authors.lastname: Quadrifoglio
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tell
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D003599:Cytoskeleton / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000502:physiology*; D003627:Data Interpretation, Statistical; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D018384:Oxidative Stress; D040901:Proteomics / Q000379:methods*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051766:Early Growth Response Protein 1; D034741:RNA, Small Interfering; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase