P73 plays a role in erythroid differentiaion through GATA1 induction

Abstract

The TP73 gene gives rise to transactivation domain-p73 isoforms (TAp73) as well as ΔNp73 variants with a truncated N terminus. Although TAp73α and -Β proteins are capable of inducing cell cycle arrest, apoptosis, and differentiation, ΔNp73 acts in many cell types as a dominant-negative repressor of p53 and TAp73. It has been proposed that p73 is involved in myeloid differentiation, and its altered expression is involved in leukemic degeneration. However, there is little evidence as to which p73 variants (TA or ΔN) are expressed during differentiation and whether specific p73 isoforms have the capacity to induce, or hinder, this differentiation in leukemia cells. In this study we identify GATA1 as a direct transcriptional target of TAp73α. Furthermore, TAp73α induces GATA1 activity, and it is required for erythroid differentiation. Additionally, we describe a functional cooperation between TAp73 and ΔNp73 in the context of erythroid differentiation in human myeloid cells, K562 and UT-7. Moreover, the impaired expression of GATA1 and other erythroid genes in the liver of p73KO embryos, together with the moderated anemia observed in p73KO young mice, suggests a physiological role for TP73 in erythropoiesis.