Genome-wide analysis and proteomic studies reveal APE1/Ref-1 multifunctional role in mammalian cells.
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.
Vascotto
Carlo
C
Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy.
Cesaratto
Laura
L
Zeef
Leo A H
LA
Deganuto
Marta
M
D'Ambrosio
Chiara
C
Scaloni
Andrea
A
Romanello
Milena
M
Damante
Giuseppe
G
Taglialatela
Giulio
G
Delneri
Daniela
D
Kelley
Mark R
MR
Mitra
Sankar
S
Quadrifoglio
Franco
F
Tell
Gianluca
G
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
D051766:Early Growth Response Protein 1; D034741:RNA, Small Interfering; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase