Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression

Jihe Zhao, Z. Christine Bian, Kristine Yee, Benjamin P C Chen, Shu Chien, Jun Lin Guan

Research output: Contribution to journalArticle

129 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1503-1515
Number of pages13
JournalMolecular Cell
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2003

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Focal Adhesion Protein-Tyrosine Kinases
Cyclin D1
Cell Cycle
Transcription Factors
Cell Adhesion
Integrins
Small Interfering RNA
Transcriptional Activation
Cell Movement

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression. / Zhao, Jihe; Bian, Z. Christine; Yee, Kristine; Chen, Benjamin P C; Chien, Shu; Guan, Jun Lin.

In: Molecular Cell, Vol. 11, No. 6, 01.06.2003, p. 1503-1515.

Research output: Contribution to journalArticle

Zhao, Jihe ; Bian, Z. Christine ; Yee, Kristine ; Chen, Benjamin P C ; Chien, Shu ; Guan, Jun Lin. / Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression. In: Molecular Cell. 2003 ; Vol. 11, No. 6. pp. 1503-1515.
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