GATA-6 induces p21(Cip1) expression and G1 cell cycle arrest.
GATA transcription factors represent a family of highly conserved zinc finger proteins with tissue-specific expression patterns. Previous studies have shown that GATA-6 is expressed in vascular smooth muscle cells (VSMCs) and rapidly down-regulated when VSMCs are induced to proliferate. Here we investigated whether the GATA-6 transcription factor can modulate cellular proliferation. Transient transfection with a GATA-6 expression vector inhibited S-phase entry in VSMCs and in mouse embryonic 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 to p53-deficient MEFs and VSMCs, MEFs null for both p21 alleles were refractory to the GATA-6-induced growth inhibition. These data demonstrate that elevated GATA-6 expression can promote the quiescent phenotype in VSMCs.
Perlman
H
H
Program in Cell, Molecular, and Developmental Biology, Tufts University, Sackler School of Biomedical Studies, Boston, Massachusetts 02111, USA.
Suzuki
E
E
Simonson
M
M
Smith
R C
RC
Walsh
K
K
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D015342:DNA Probes; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016193:G1 Phase; D050993:GATA6 Transcription Factor; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D016335:Zinc Fingers
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; C494760:Gata6 protein, mouse; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA