The transcription factor ATF3 is upregulated during chondrocyte differentiation and represses cyclin D1 and A gene transcription.
The transcription factor ATF3 is upregulated during chondrocyte differentiation and represses cyclin D1 and A gene transcription.
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DOI：
10.1186/1471-2199-7-30
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发表时间：
2006-09-19
影响因子：
--
通讯作者：
Beier F
中科院分区：
文献类型：
--
作者：
James CG;Woods A;Underhill TM;Beier F
协调的软骨细胞增殖和分化是正常软骨内骨生长所必需的。已知与cyclicAMP应答元件（CRE）结合的转录因子可调节这些过程。该家族的一个成员，激活转录因子3 (ATF3)，在骨骼形成过程中表达，并作为转录抑制因子，但该蛋白在软骨形成中的功能尚不清楚。在这里，我们证明了Atf3 mRNA水平在体外和体内小鼠软骨细胞分化过程中增加。此外，Atf3 mRNA水平在细胞松弛素D（一种软骨细胞成熟的诱导剂）的作用下升高。这伴随着细胞松弛素d处理的软骨细胞中Atf3启动子活性的增加。我们之前已经证明，软骨细胞中细胞周期基因cyclin D1和cyclin A的转录依赖于cre。在这里，我们证明了ATF3在小鼠原代软骨细胞中的过表达会导致这两个基因的转录减少，以及CRE报告质粒的活性降低。ATF3抑制周期蛋白A转录需要周期蛋白A启动子中的CRE。与此同时，ATF3过表达会降低sox9依赖性启动子的活性，并增加runx2依赖性启动子的活性。我们的数据表明，成熟软骨细胞中Atf3基因的转录诱导导致cyclin D1和cyclin A表达下调以及runx2依赖性转录的激活。因此，ATF3诱导似乎促进了软骨细胞的细胞周期退出和终末分化。
Coordinated chondrocyte proliferation and differentiation are required for normal endochondral bone growth. Transcription factors binding to the cyclicAMP response element (CRE) are known to regulate these processes. One member of this family, Activating Tanscription Factor 3 (ATF3), is expressed during skeletogenesis and acts as a transcriptional repressor, but the function of this protein in chondrogenesis is unknown. Here we demonstrate that Atf3 mRNA levels increase during mouse chondrocyte differentiation in vitro and in vivo. In addition, Atf3 mRNA levels are increased in response to cytochalasin D treatment, an inducer of chondrocyte maturation. This is accompanied by increased Atf3 promoter activity in cytochalasin D-treated chondrocytes. We had shown earlier that transcription of the cell cycle genes cyclin D1 and cyclin A in chondrocytes is dependent on CREs. Here we demonstrate that overexpression of ATF3 in primary mouse chondrocytes results in reduced transcription of both genes, as well as decreased activity of a CRE reporter plasmid. Repression of cyclin A transcription by ATF3 required the CRE in the cyclin A promoter. In parallel, ATF3 overexpression reduces the activity of a SOX9-dependent promoter and increases the activity of a RUNX2-dependent promoter. Our data suggest that transcriptional induction of the Atf3 gene in maturing chondrocytes results in down-regulation of cyclin D1 and cyclin A expression as well as activation of RUNX2-dependent transcription. Therefore, ATF3 induction appears to facilitate cell cycle exit and terminal differentiation of chondrocytes.
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影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
--
作者：
Beier, F;Luvalle, P
通讯作者：
Luvalle, P
DOI：
10.1159/000157093
发表时间：
1988-01-01
期刊：
PATHOLOGY AND IMMUNOPATHOLOGY RESEARCH
影响因子：
--
作者：
BENYA, PD
通讯作者：
BENYA, PD
影响因子：
7.4
作者：
Bakin, AV;Stourman, NV;Freeman, ML
通讯作者：
Freeman, ML
哺乳动物转录因子 ATF6 以跨膜蛋白的形式合成，并在内质网应激时通过蛋白水解激活
影响因子：
3.3
作者：
Haze, K;Yoshida, H;Mori, K
通讯作者：
Mori, K