Submitted October 1, 2008
Accepted April 22, 2009
GATA-1 associates with and inhibits p53
Cecelia D. Trainor*, Caroline Mas, Patrick Archambault, Paola Di Lello, and James G. Omichinski
Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD, United States
Departement de Biochimie, Universite de Montreal, Montreal, Quebec, Canada
* Corresponding author; email: ceceliat{at}mail.nih.gov.
In addition to orchestrating the expression of all erythroid-specific genes, GATA-1 controls the growth, differentiation and survival of the erythroid lineage through the regulation of genes that manipulate the cell cycle and apoptosis. The stages of mammalian erythropoiesis include global gene inactivation, nuclear condensation and enucleation to yield circulating erythocytes, and some of the genes whose expression are altered by GATA-1 during this process are members of the p53 pathway. Here, we demonstrate a specific in vitro interaction between the transactivation domain of p53 (p53TAD) and a segment of the GATA-1 DNA-binding domain (DBD) that includes the carboxyl-terminal zinc-finger domain. We also show by immmunopercipitation that the native GATA-1 and p53 interact in erythroid cells and that activation of p53-responsive promoters in an erythroid cell line can be inhibited by the over- expression of GATA-1. Mutational analysis reveals that GATA-1 inhibition of p53 minimally requires the segment of the GATA-1 DBD that interacts with p53TAD. This inhibition is reciprocal, as the activation of a GATA-1 responsive promoter can be inhibited by p53. Based on these findings, we conclude that inhibition of the p53 pathway by GATA-1 may be essential for erythroid cell development and survival.
