INVESTIGADORES
CANEPA Eduardo Tomas
congresos y reuniones científicas
Título:
Multiple kinases are involved in p19INK4d induction and phosphorylation in response to genotoxics
Autor/es:
MARIA F. OGARA; MARIELA C. MARAZITA; MARIA E. SCASSA; EDUARDO T. CANEPA
Lugar:
Rosario, Provincia de Santa F¨¦
Reunión:
Congreso; XLII Reuni¨®n Anual de la Sociedad Argentina de Investigaci¨®n en Bioqu¨ªmica y Biolog¨ªa Molecular; 2006
Institución organizadora:
Sociedad Argentina de Investigaci¨®n en Bioqu¨ªmica y Biolog¨ªa Molecular
Resumen:
ST-C03
MULTIPLE KINASES ARE INVOLVED IN p19INK4d
INDUCTION AND PHOSPHORYLATION IN RESPONSE
TO GENOTOXICS
Ogara, M.F.; Marazita, M.C.; Scassa, M. E.; C¨¢nepa, Eduardo T.
Laboratorio Biolog¨ªa Molecular, Dpto. Qu¨ªmica Biol¨®gica, FCEN,
UBA, Bs Aires, Argentina. E-mail: flopyogara@qb.fcen.uba.ar
p19INK4d belongs to a family of cyclin-dependent kinase
inhibitors that arrests cells in G1 interacting with CDK4/6. This
protein participates in the cellular response to genotoxic stress,
enhancing DNA repair and lowering apoptosis. Upon genotoxic
insult, p19 is induced and subject to phosphorylation. As p19
phosphorylation is necessary for its role in DNA repair, we
sought to characterize the signal transduction pathways leading
to p19 activation and induction in WI38 diploid human fibroblasts
exposed to the following genotoxic agents: UVC irradiation, the
antitumoral cisplatin, or ¦Â-amyloid peptide. Northern blot analysis
and immunoprecipitation assays following metabolic labeling with
[32P]orthophosphate revealed that inhibition of ATM/ATR by
caffeine 5 mM or specific inhibition of Chk1 blocks p19 induction
and phosphorylation. Depending on the type of DNA lesion,
impairment of Chk2 activity suppressed p19 phosphorylation
without affecting its mRNA levels. None of the studied kinases
MAPK, PI3K, PKA o CDKs seem to be implicated in the
regulation of p19 in response to DNA damage. However, PKA or
CDKs activity abrogation, partially or totally, respectively, blocked
its phosphorylation. Our results demonstrate that, apart from
ATM/ATR activation, different mechanisms would exist for the
control of the expression and activity of p19 that vary according
to the type of injury.