Modulation of Sp1 activity by a cyclin A/CDK complex
Modulation of Sp1 activity by a cyclin A/CDK complex
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DOI：
10.1006/jmbi.2000.4406
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发表时间：
2001-02-16
影响因子：
5.6
通讯作者：
Rotheneder, H
中科院分区：
文献类型：
--
作者：
Haidweger, E;Novy, M;Rotheneder, H
Sp1 家族的转录因子是多种调控途径的靶标，可以诱导或抑制基因表达。在这里，我们证明 Sp1 与组蛋白 1 激酶活性相关。该活性受生长调节并与细胞周期蛋白 A 的表达相关。免疫共沉淀实验表明，Sp1 与细胞周期蛋白 A 相互作用，并且可以被细胞周期蛋白 A 相关激酶磷酸化。这种相互作用是直接的，需要 Sp1 的锌指区域和细胞周期蛋白 A 的氨基末端结构域。细胞周期蛋白 A 的过表达会增强由 Spl 响应启动子控制的报告基因的表达。另一方面，添加奥洛穆辛（CDK2 和 CDC2 活性的特异性抑制剂）会降低报告基因的表达。电泳迁移率变动分析表明这是由于 Sp1 家族成员的 DNA 结合能力降低所致。我们的结果表明，细胞周期蛋白 A/CDK 复合物对 Sp1 和该家族其他成员的磷酸化可能在其转录活性的生长和细胞周期调节中发挥作用。 (C) 2001 年学术出版社。
Transcription factors of the Sp1 family are targets of several regulatory pathways and can induce or inhibit gene expression. Here we show that Sp1 is associated with a histone 1 kinase activity. This activity is growth regulated and correlates with the expression of cyclin A. Co-immunoprecipitation experiments demonstrate, that Sp1 interacts with cyclin A and can be phosyhorylated by a cyclin A associated kinase. The interaction is direct and requires the zinc-finger region of Sp1 and the aminoterminal domain of cyclin A. Over-expression of cyclin A enhances the expression of a reporter gene controlled by an Spl responsive promoter. Addition of olomoucine, a specific inhibitor of CDK2 and CDC2 activity on the other hand reduces the expression of the reporter. Electrophoretic mobility shift assays suggest that this is due to a reduction of the DNA binding ability of Sp1 family members. Our results indicate that phosphorylation of Sp1 and other members of the family by a cyclin A/CDK complex may play a role in the growth and cell cycle regulation of its transcriptional activity. (C) 2001 Academic Press.