INVESTIGADORES
CERUTI Julieta Maria
congresos y reuniones científicas
Título:
E2F MEDIATED INDUCTION OF P19INK4D PLAYS AN IMPORTANT ROLE IN CELL CYCLE AND DNA DAMAGE RESPONSE
Autor/es:
CARCAGNO, AL; SONZOGNI, SG; CERUTI, JM; GIONO, LE; CÁNEPA, ET
Lugar:
Villa Carlos Paz. Argentina
Reunión:
Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008
Institución organizadora:
SAIB
Resumen:
E2F MEDIATED INDUCTION OF P19INK4D PLAYS AN
IMPORTANT ROLE IN CELL CYCLE AND DNA DAMAGE
RESPONSE
p19INK4 is a member of the INK4 family of proteins that regulate
G1/S cell cycle transition. INK4s inhibit pRb phosphorylation by
CDK 4/6 and consequently reduce the transcriptional activity of
E2F. p19 is expressed periodically during the cell cycle, showing
the highest level at the G1/S phase. In silico analysis of the p19
promoter sequence revealed potential E2F binding sites. Moreover,
the overexpression of E2F in asynchronic fibroblasts led to an
increase in p19 mRNA at all cell cycle phases. However, the
physiological significance of p19 regulation by E2F remained to be
explored. The aim of this work was to study the role of E2F in two
aspects of p19 expression: its periodic regulation during the cell
cycle and its induction during the DNA damage response. To
achieve this, we developed a strategy based on triple helix-forming
oligonucleotides (TFOs) in order to prevent E2F binding to its
response elements in the p19 promoter. Proof of principle
experiments showed that TFOs were able to specifically prevent
p19 induction by E2F during normal cell cycle as well as following
DNA damage. In subsequent experiments, TFOs transfected cells
showed alterations in their cell cycle kinetics, proliferation and
ability to repair damaged DNA (clonogenicity). These results
highlight the significance of the regulation of p19 by E2F in
different physiological situations.