1. Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression
- Author
-
Z. Christine Bian, Benjamin P C Chen, Jun-Lin Guan, Jihe Zhao, Shu Chien, and Kristine Yee
- Subjects
Transcriptional Activation ,Integrins ,Transcription, Genetic ,Cyclin D ,Cyclin A ,Cyclin B ,Kruppel-Like Transcription Factors ,Focal adhesion ,Mice ,Cyclin D1 ,Genes, Reporter ,Animals ,RNA, Small Interfering ,Cell adhesion ,Promoter Regions, Genetic ,Molecular Biology ,Transcription factor ,Cells, Cultured ,Sequence Deletion ,Cell Nucleus ,Cyclin-dependent kinase 1 ,Binding Sites ,biology ,Cell Cycle ,Antibodies, Monoclonal ,Cell Biology ,3T3 Cells ,Protein-Tyrosine Kinases ,Cell biology ,Gene Expression Regulation ,Focal Adhesion Kinase 1 ,Focal Adhesion Protein-Tyrosine Kinases ,Mutation ,Cancer research ,biology.protein ,Protein Binding ,Signal Transduction ,Transcription Factors - Abstract
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 ΔC14. 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.
- Published
- 2003