GATA-6 Induces p21Cip1 Expression and G1Cell Cycle Arrest*
- From the ‡Program in Cell, Molecular, and Developmental Biology, Tufts University, Sackler School of Biomedical Studies, Boston, Massachusetts 02111, the §Division of Cardiovascular Research, St. Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, and the‖Division of Nephrology, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106
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.
Footnotes
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↵* This work was supported by National Institutes of Health Grants AR-40197 and HL-50692 (to K. W.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ Current address: The Second Dept. of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku Tokyo 113, Japan.
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↵** To whom correspondence should be addressed: Division of Cardiovascular Research, St. Elizabeth’s Medical Center, 736 Cambridge St., Boston, MA 02135. Tel.: 617-562-7501; Fax: 617-562-7506; E-mail:kwalsh{at}opal.tufts.edu.
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↵1 The abbreviations used are: VSMC(s), vascular smooth muscle cell(s); DMEM, Dulbecco’s modified Eagle’s medium; FBS, fetal bovine serum; PBS, phosphate-buffered saline; DPBS, Dulbecco’s PBS; BrdUrd, 5-bromo-2-deoxyuridine; MEF(s), mouse embryonic fibroblast(s).
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- Received November 10, 1997.
- Revision received January 19, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
