Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression
Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression
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DOI：
10.1016/s1097-2765(03)00179-5
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发表时间：
2003-06-01
期刊：
影响因子：
16
通讯作者：
Guan, JL
中科院分区：
文献类型：
--
作者：
Zhao, JH;Bian, ZC;Guan, JL
局灶黏附激酶（Focal adhesion kinase， FAK）是整合素信号传导调控细胞黏附、迁移、存活和增殖的重要媒介。在这里，我们报道了转录因子KLF8作为FAK在细胞周期调控中的靶标的鉴定。KLF8由FAK诱导，并被FAK显性阴性突变体DeltaC14抑制。KLF8的过表达增加了细胞周期的进展，而siRNA抑制内源性KLF8则减少了细胞周期的进展。Cyclin D1启动子被确定为KLF8的靶标，KLF8通过与GT box a结合直接激活，并通过间接机制抑制Cyclin D1的潜在抑制调节因子。FAK对cyclin D1的转录激活需要Ets家族和KLF8因子在时间上的差异。总之，我们的数据为FAK调节细胞周期进程的分子机制提供了进一步的见解。
Focal adhesion kinase (FAK) is an important mediator of integrin signaling in the regulation of cell adhesion, migration, survival, and proliferation. Here we report the identification of the transcription factor KLF8 as a target of FAK in cell cycle regulation. KLF8 is induced by FAK and decreased by FAK dominant-negative mutant DeltaC14. Overexpression of KLF8 increases cell cycle progression, whereas inhibition of endogenous KLF8 by siRNA reduces it. Cyclin D1 promoter is identified as a target of KLF8, which is activated both directly by KLF8 binding to the GT box A and by an indirect mechanism through its repression of a potential inhibitory regulator of cyclin D1. Transcription activation of cyclin D1 by FAK requires both Ets family and KLF8 factors in a temporally differential manner. Together, our data provide further insights into molecular mechanism for FAK to regulate cell cycle progression.