Egr-1 induces p19 expression in neural type cells

LAURA BYK; MARIELA MARAZITA; ABEL CARCAGNO; EDUARDO CÁNEPA

San miguel de Tucumán, Argentina.

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Neuronal terminal differentiation is directly linked to cell cycle exit. Previous data suggests that two CDK inhibitors, p19INK4d and p27Kip1, are responsible for neural postmitotic arrest. Why both proteins show early expression during the central nervous system development and their levels remain high even in adulthood is still to be determined. The aim of this work is to study the mechanisms that are implicated on maintaining the high levels of p19 in terminal differentiated neurons. For this, SH-SY5Y and HN9 cells were treated or not with retinoic acid to induce differentiation, and p19 mRNA stability was analyzed by northern blot after treatment with actinomycin D. This experiment showed that p19 half-life on differentiated cells doubles that of cells in G1/S. Moreover, we observed that EGR-1, a transcription factor involved in the neuronal differentiation process, causes a 2.5-fold induction on p19 levels. Of note, several potential EGR-1 binding sites were found on the p19 promoter, suggesting a direct effect. Our results indicate that an increased transcription of p19, mediated by EGR-1, added to an enhanced mRNA stability, could contribute to the elevated expression levels of p19 in postmitotic neurons.