Activation of the rat cyclin a promoter by ATF2 and Jun family members and its suppression by ATF4
Activation of the rat cyclin a promoter by ATF2 and Jun family members and its suppression by ATF4
复制标题
DOI：
10.1006/excr.1997.3884
复制
发表时间：
1998-02-25
影响因子：
3.7
通讯作者：
Oda, K
中科院分区：
文献类型：
--
作者：
Shimizu, M;Nomura, Y;Oda, K
细胞周期蛋白A（Cyclin A）在细胞周期的G_1期向S期转变过程中起重要作用，在G_0期和G_1期cyclin A的表达受到抑制，而在G_1/S期的表达受到强烈的诱导。对大鼠cyclin A启动子5'端序列缺失衍生物与荧光素酶cDNA融合的分析表明，ATF/CRE基序主要决定G_1/S期的诱导。在ATP/CRE位点形成的复合物的凝胶位移分析表明，该复合物不与G 0/G1细胞提取物形成，但最大限度地与晚期GI细胞提取物形成。该复合物被抗JunD抗体超位移，并且用抗JunD抗体制备的免疫复合物的Western印迹分析揭示了ATF 2的存在，表明JunD与ATF 2的异源二聚化。在静止状态的大鼠3 Y1细胞中，共转染编码ATP 2和Jun家族成员的表达质粒可使报告质粒中的cyclin A启动子激活近10倍，而共转染编码ATP 4的表达质粒则抑制ATP 2和Jun家族成员介导的启动子激活。Jun家族成员的表达在G1早期和晚期呈双相性，在G1/S期Jun D的表达明显增加，ATP家族成员的表达沿着增加。这些结果表明，细胞周期蛋白A启动子活性的调节，至少部分，由ATF和Jun家族成员的相对量。(C)北京：科学出版社.
Cyclin A plays an essential role in the G1 to S phase transition in the cell cycle, The expression of cyclin A is restrained during GO and G1, but steeply induced at the G1/S boundary, Analysis of the rat cyclin A promoter elements with the 5' sequential deletion derivatives of the promoter fused to the luciferase cDNA indicated that the ATF/CRE motif primarily determines the inducibility at G1/S. Gel shift analysis of the complex formed at the ATP/CRE site indicated that the complex was not formed with the G0/G1 cell extract, but maximally formed with the late-GI cell extract, The complex was supershifted by anti-JunD antibody, and Western blot analysis of the immune complexes prepared with anti-JunD antibody revealed the presence of ATF2, suggesting heterodimerization of JunD with ATF2. The cyclin A promoter in a reporter plasmid was activated by nearly 10-fold in quiescent rat 3Y1 cells by cotransfection with the expression plasmids encoding ATF2 and Jun family members, In contrast, cotransfection with the ATF4 expression plasmid suppressed the promoter activation mediated by ATP2 and Jun family members. The expression of Jun family members during G1 to S progression was induced biphasically in early and late G1 and the level of JunD increased markedly at the G1/S, while that of ATP family members was gradually increased along with the G1 to S progression. These results indicate that the cyclin A promoter activity is regulated, at least in part, by relative amounts of the ATF and Jun family members. (C) 1998 Academic Press.