GATA-6 induces p21Cip1 expression and G1 cell cycle arrest

被引:101
作者
Perlman, H
Suzuki, E
Simonson, M
Smith, RC
Walsh, K
机构
[1] Tufts Univ, Sch Med, St Elizabeths Med Ctr, Div Cardiovasc Res, Boston, MA 02135 USA
[2] Tufts Univ, Sackler Sch Biomed Studies, Program Cell Mol & Dev Biol, Boston, MA 02111 USA
[3] Case Western Reserve Univ, Dept Med, Div Nephrol, Cleveland, OH 44106 USA
关键词
D O I
10.1074/jbc.273.22.13713
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:13713 / 13718
页数:6
相关论文
共 47 条
[1]  
CAMPBELL GR, 1988, ARCH PATHOL LAB MED, V112, P977
[2]  
CAMPBELL GR, 1987, VASCULAR SMOOTH MUSC, V1, P39
[3]   ADENOVIRUS-MEDIATED OVER-EXPRESSION OF THE CYCLIN CYCLIN-DEPENDENT KINASE INHIBITOR, P21 INHIBITS VASCULAR SMOOTH-MUSCLE CELL-PROLIFERATION AND NEOINTIMA FORMATION IN THE RAT CAROTID-ARTERY MODEL OF BALLOON ANGIOPLASTY [J].
CHANG, MW ;
BARR, E ;
LU, MM ;
BARTON, K ;
LEIDEN, JM .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (05) :2260-2268
[4]   Downregulation of cyclin-dependent kinase 2 activity and cyclin a promoter activity in vascular smooth muscle cells by p27(KIP1), inhibitor of neointima formation in the rat carotid artery [J].
Chen, DH ;
Krasinski, K ;
Chen, DF ;
Sylvester, A ;
Chen, J ;
Nisen, PD ;
Andres, V .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (10) :2334-2341
[5]  
Clayman GL, 1996, ARCH OTOLARYNGOL, V122, P489
[6]   THE GROWTH ARREST-SPECIFIC GENE, GAS1, IS INVOLVED IN GROWTH SUPPRESSION [J].
DELSAL, G ;
RUARO, ME ;
PHILIPSON, L ;
SCHNEIDER, C .
CELL, 1992, 70 (04) :595-607
[7]   MICE LACKING P21(C/P1/WAF1) UNDERGO NORMAL DEVELOPMENT, BUT ARE DEFECTIVE IN G1 CHECKPOINT CONTROL [J].
DENG, CX ;
ZHANG, PM ;
HARPER, JW ;
ELLEDGE, SJ ;
LEDER, P .
CELL, 1995, 82 (04) :675-684
[8]   WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION [J].
ELDEIRY, WS ;
TOKINO, T ;
VELCULESCU, VE ;
LEVY, DB ;
PARSONS, R ;
TRENT, JM ;
LIN, D ;
MERCER, WE ;
KINZLER, KW ;
VOGELSTEIN, B .
CELL, 1993, 75 (04) :817-825
[9]   MAMMALIAN GENES COORDINATELY REGULATED BY GROWTH ARREST SIGNALS AND DNA-DAMAGING AGENTS [J].
FORNACE, AJ ;
NEBERT, DW ;
HOLLANDER, MC ;
LUETHY, JD ;
PAPATHANASIOU, M ;
FARGNOLI, J ;
HOLBROOK, NJ .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (10) :4196-4203
[10]   MOLECULAR-CLONING OF A DIVERGED HOMEOBOX GENE THAT IS RAPIDLY DOWN-REGULATED DURING THE G(0)/G(1) TRANSITION IN VASCULAR SMOOTH-MUSCLE CELLS [J].
GORSKI, DH ;
LEPAGE, DF ;
PATEL, CV ;
COPELAND, NG ;
JENKINS, NA ;
WALSH, K .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (06) :3722-3733