INVESTIGADORES
CANEPA Eduardo Tomas
artículos
Título:
E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation
Autor/es:
ABEL C. CARCAGNO; LUCIANA E. GIONO; MARIELA C. MARAZITA; DANIELA S. CASTILLO; NICOLÁS PREGI; EDUARDO T. CÁNEPA
Revista:
MOLECULAR AND CELLULAR BIOCHEMISTRY
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2012
ISSN:
0300-8177
Resumen:
Abstract Central to the maintenance of genomic integrity
is the cellular DNA damage response. Depending on
the type of genotoxic stress and through the activation of
multiple signaling cascades, it can lead to cell cycle arrest,
DNA repair, senescence, and apoptosis. p19INK4d, a
member of the INK4 family of CDK inhibitors, plays a
dual role in the DNA damage response, inhibiting cell
proliferation and promoting DNA repair. Consistently,
p19INK4d has been reported to become upregulated in
response to UV irradiation and a great variety of genotoxic
agents. Here, this induction is shown to result from a
transcriptional stimulatory mechanism that can occur at
every phase of the cell cycle except during mitosis.
Moreover, evidence is presented that demonstrates that
E2F1 is involved in the induction of p19INK4d following
UV treatment, as it is prevented by E2F1 protein ablation
and DNA-binding inhibition. Specific inhibition of this
regulation using triplex-forming oligonucleotides that target
the E2F response elements present in the p19INK4d
promoter also block p19INK4d upregulation and sensitize
cells to DNA damage. These results constitute the first
description of a mechanism for the induction of p19INK4d
in response to UV irradiation and demonstrate the physiological
relevance of this regulation following DNA
damage.