p53 Heme Oxygenase 1 crosstalk in embryonic stem cells

NICOLÁS ANSELMINO; VICTORIA PETRONE; ALEJANDRA GUBERMAN; CLAUDIA SOLARI; MARCOS FRANCIA; AYELEN TORO; CAMILA VÁZQUEZ ECHEGARAY; ELBA VÁZQUEZ

buenos aires

Congreso; Xth Meeting of the Latin American Society for Developmental Biology; 2019

LASDB

Embryonic stem cells (ESCs) are widely exploited to model early embryo development. Reactive oxygen species (ROS) balance in ESCs is relevant both for pluripotency and differentiation. Heme Oxygenase 1 (HO-1) is an antioxidant protein essential to redox homeostasis. On the other hand, p53, besides its classical function in response to DNA damage, is involved in ROS generation. Although the relationship between these proteins has been explored, little is known about their connection in ESCs. We aimed to study how the crosstalk between HO-1 and p53 influences ESCs fundamental properties. In this work, we focused in HO-1 gene regulation by p53. We have previously found that HO-1 protein levels were increased in a p53-/- ESC line generated in our lab. Notably, RNA levels were not altered suggesting that HO-1 protein stability is regulated by p53 in ESC. To delve into the mechanism involved we evaluated the effect of protein inhibition by cycloheximide in HO-1 gene modulation. We found higher HO-1 half-life in the knockout cell line respect to the wt. Remarkably, HO-1 transcription increased in response to hemin treatment or differentiation stimulus in p53-/- cells similar to wt, evidencing different levels of HO-1 gene regulation in ESCs. We are currently studying if HO-1 protein stability involves differential p53-dependent proteasome-mediated proteolysis. A p53-HO-1 crosstalk could evidence a link between different stress response pathways relevant to ESC survival and differentiation.