Involvement of p19INK4d in replicative senescence

SILVINA V. SONZOGNI; LAURA BYK; EDUARDO T. CÁNEPA

San Miguel de Tucumán

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biologia Molecular; 2009

Sociedad Argentina de Investigación en Bioquímica y Biologia Molecular

INVOLVEMENT OF p19INK4D IN REPLICATIVE SENESCENCE Silvina V. Sonzogni, Laura A. Byk, and Eduardo T. Cánepa Laboratorio de Biología Molecular-Depto Química Biológica-FCEN-UBA-Ciudad Universitaria-Buenos Aires Senescence is a cellular program that leads to an irreversible cell cycle arrest and is accompanied by phenotypic changes. This mechanism is activated in response to physiological aging and different types of stress. The factors responsible for establishing cellular senescence are pRb and p53. However, the factors involved in its maintenance, as well as those that determine cell fate, apoptosis or senescence, are still unknown. We have demonstrated that p19INK4d, a member of the INK4 family, is upregulated in response to stress-induced senescence, suggesting that p19 might play a role in this process. The aim of this work is to study the involvement of p19 in replicative senescence. Primary fibroblasts from human and mouse enter replicative senescence after 5 to 10 passages and were used as a cellular system for this work. Both p19 mRNA and protein levels became upregulated from passage 5 onward. Increased transcription of the p19 promoter was confirmed by gene reporter and run-on experiments. The E2F1 transcription factor, that is involved in the induction of p19 following stress-induced senescence, does not play a role in replicative senescence, indicating the existence of different pathways. In both cases, however, the response appears to be ATM/ATR-dependent. Our results support a role for p19 in replicative senescence, in addition to that induced by genotoxic drugs.