GATA-6 INDUCES P21(CIP1) EXPRESSION AND G(1) CELL-CYCLE ARREST

GATA transcription factors represent a family of highly conserved zinc finger proteins with tissue-specific expression patterns. Previous st udies have shown that GATA-6 is expressed in vascular smooth muscle ce lls (VSMCs) and rapidly down-regulated when VSMCs are induced to proli ferate. Here we investigated whether the GATA-6 transcription factor c an modulate cellular proliferation. Transient transfection with a GATA -6 expression vector inhibited S-phase entry in VSMCs and in mouse emb ryonic fibroblasts (MEFs) lacking both p53 alleles. The GATA-6-induced growth arrest correlated with a marked increase in the expression of the general cyclin dependent kinase (Cdk) inhibitor p21. In contrast t o p53-deficient MEFs and VSMCs, MEFs null for both p21 alleles were re fractory to the GATA-6-induced growth inhibition. These data demonstra te that elevated GATA-6 expression can promote the quiescent phenotype in VSMCs.