GATA-6 induces p21(Cip1) expression and G1 cell cycle arrest.

H Perlman, E Suzuki, M Simonson, R C Smith, K Walsh
Author Information
  1. H Perlman: Program in Cell, Molecular, and Developmental Biology, Tufts University, Sackler School of Biomedical Studies, Boston, Massachusetts 02111, USA.

Abstract

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.

Grants

  1. AR-40197/NIAMS NIH HHS
  2. HL-50692/NHLBI NIH HHS

MeSH Term

Animals
Base Sequence
Cell Differentiation
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
DNA
DNA Probes
DNA Replication
DNA-Binding Proteins
G1 Phase
GATA6 Transcription Factor
Humans
Mice
Mice, Knockout
Muscle, Smooth, Vascular
Protein Binding
Sequence Deletion
Transcription Factors
Tumor Suppressor Protein p53
Zinc Fingers

Chemicals

CDKN1A protein, human
Cdkn1a protein, mouse
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
DNA Probes
DNA-Binding Proteins
GATA6 Transcription Factor
GATA6 protein, human
Gata6 protein, mouse
Transcription Factors
Tumor Suppressor Protein p53
DNA

Word Cloud

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