@article{2660cc8c3db34f2694653ecae2ee7270,
title = "Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression",
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.",
author = "Jihe Zhao and Bian, {Z. Christine} and Kristine Yee and Chen, {Benjamin P C} and Shu Chien and Guan, {Jun Lin}",
note = "Funding Information: We are grateful to Dr. K. Peck of Institute of Biomedical Sciences, Taipei, ROC for Nylon membranes with cDNA microarrays; Dr. R. Pestell of Albert Einstein College of Medicine, NY for the cyclin D1 promoter reporter construct; Dr. T Hunter of Salk Institute, CA for pRK5-D1 construct; Dr. D. Ilic of University of California, San Francisco, CA for FAK −/− and control cells; and Dr. R. Levine of Cornell University for the EF1α cDNA. We are also very grateful to Drs. Paul Higgins and Mike DiPersio of Albany Medical College for generously providing their lab space, some reagents, and help during part of the studies. We thank Xu Peng, Tang-Long Shen, Luis Rodriguez, Lee Ann Cooper, Boyi Gan, Dan Rhoads, Xiaoyang Wu, and Richard Liang for their critical reading of the manuscript and helpful comments. This research was supported by NIH grants to J.G. and S.C.",
year = "2003",
month = jun,
day = "1",
doi = "10.1016/S1097-2765(03)00179-5",
language = "English (US)",
volume = "11",
pages = "1503--1515",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}