Variations in Jun and Fos protein expression and AP-1 activity in cycling, resting and stimulated fibroblasts

Variations in Jun and Fos protein expression and AP-1 activity in cycling, resting and stimulated fibroblasts
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DOI:
10.1038/sj.onc.1200901
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发表时间:
1997-02-20
期刊:
影响因子:
8
通讯作者:
Pfarr, CM
Pfarr, CM
中科院分区:
医学1区
文献类型:
--
作者:
Lallemand, D;Spyrou, G;Pfarr, CM

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我们分析了不同的Jun和Fos蛋白质作为NIH 3 T3成纤维细胞从指数生长到静止,并在血清刺激后重新进入细胞周期后的第一个24小时内,我们表明,这些蛋白质可以分为3个亚组的基础上,他们的表达模式。第一个包含c-Jun、Jun-D和Fra-2,它们在循环细胞中以高水平表达,并且仅被血清轻度诱导。第二类含有Jun-B、c-Fos、Fos-B和Delta Fos-B,它们在周期细胞中的水平较低,但在血清刺激后强烈而迅速地增加。第三组仅含有Fra-1,其不存在于循环细胞中,并且在血清刺激后表现为延迟的早期反应蛋白,AP-1结合活性在循环和静止成纤维细胞中均较低,但在血清刺激后增加,其动力学与各种Jun和Fos蛋白的诱导相匹配。抗体超位移分析表明,AP-I结合活性的组成反映了每个Jun和Fos蛋白的相对丰度。此外,随着生长条件的变化,所有AP-1蛋白的翻译后修饰状态连续变化。这些数据表明,AP-1活性在G(0)-G(1)转换过程中受到精细调控和复杂,涉及蛋白质表达和翻译后修饰的变化。
We have analysed the different Jun and Fos proteins as NIH3T3 fibroblasts pass from exponential growth to quiescence and during the first 24 h after their re-entry into the cell cycle following serum stimulation, We show that these proteins can be divided into 3 subgroups based on their pattern of expression. The first contains c-Jun, Jun-D and Fra-2 which are expressed at high level in cycling cells and are only mildly induced by serum. The second contains Jun-B, c-Fos, Fos-B and Delta Fos-B whose levels are low in cycling cells but increase strongly and rapidly after stimulation by serum. The third group contains only Fra-1, which is absent from cycling cells and behaves as a delayed early response protein after serum stimulation, AP-I binding activity is low both in cycling and quiescent fibroblasts but increases after stimulation by serum with kinetics matching the induction of the various Jun and Fos proteins. Antibody supershift analyses demonstrate that the composition of AP-I binding activity reflects the relative abundance of each Jun and Fos protein. Furthermore, the state of post-translational modification varies continuously for all of the AP-1 proteins as growth conditions change. These data indicate that AP-1 activity during the G(0)-G(1) transition is finely regulated and complex, involving changes both in protein expression and in posttranslational modification.