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Mol. Cells 2013; 36(1): 1-6

Published online July 31, 2013

https://doi.org/10.1007/s10059-013-0139-1

© The Korean Society for Molecular and Cellular Biology

Nuclear FAK: a New Mode of Gene Regulation from Cellular Adhesions

Ssang-Taek Steve Lim

Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, USA

Received: May 3, 2013; Accepted: May 6, 2014

Abstract

Focal adhesion kinase (FAK) is a protein tyrosine kinase (PTK) crucial in regulation of cell migration and proliferation. In addition to its canonical roles as a cytoplasmic kinase downstream of integrin and growth factor receptor signaling, recent studies revealed new aspects of FAK action in the nucleus. Nuclear FAK promotes p53 and GATA4 degradation via ubiquitination, resulting in enhanced cell proliferation and reduced inflammatory responses. FAK can also serve as a co-transcriptional regulator that alters a gene transcriptional activity. These findings established a new paradigm of FAK signaling from cellular adhesions to the nucleus. Although physiological stimuli for controlling FAK nuclear localization have not been completely characterized, FAK shuttles from focal adhesions to the nucleus to directly convey extracellular signals. Interestingly, nuclear translocation of FAK becomes prominent in kinase-inhibited conditions such as in de-adhesion and pharmacological FAK inhibition, while a small fraction of nuclear FAK is observed a normal growth condition. In this review, roles of nuclear FAK in regulating transcription factors will be discussed. Furthermore, a potential use of a pharmacological FAK inhibitor to target nuclear FAK function in diseases such as inflammation will be emphasized.

Keywords cell proliferation, FAK, FERM, GATA4, inflammation, p53

Article

Minireview

Mol. Cells 2013; 36(1): 1-6

Published online July 31, 2013 https://doi.org/10.1007/s10059-013-0139-1

Copyright © The Korean Society for Molecular and Cellular Biology.

Nuclear FAK: a New Mode of Gene Regulation from Cellular Adhesions

Ssang-Taek Steve Lim

Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, USA

Received: May 3, 2013; Accepted: May 6, 2014

Abstract

Focal adhesion kinase (FAK) is a protein tyrosine kinase (PTK) crucial in regulation of cell migration and proliferation. In addition to its canonical roles as a cytoplasmic kinase downstream of integrin and growth factor receptor signaling, recent studies revealed new aspects of FAK action in the nucleus. Nuclear FAK promotes p53 and GATA4 degradation via ubiquitination, resulting in enhanced cell proliferation and reduced inflammatory responses. FAK can also serve as a co-transcriptional regulator that alters a gene transcriptional activity. These findings established a new paradigm of FAK signaling from cellular adhesions to the nucleus. Although physiological stimuli for controlling FAK nuclear localization have not been completely characterized, FAK shuttles from focal adhesions to the nucleus to directly convey extracellular signals. Interestingly, nuclear translocation of FAK becomes prominent in kinase-inhibited conditions such as in de-adhesion and pharmacological FAK inhibition, while a small fraction of nuclear FAK is observed a normal growth condition. In this review, roles of nuclear FAK in regulating transcription factors will be discussed. Furthermore, a potential use of a pharmacological FAK inhibitor to target nuclear FAK function in diseases such as inflammation will be emphasized.

Keywords: cell proliferation, FAK, FERM, GATA4, inflammation, p53

Mol. Cells
Dec 31, 2021 Vol.44 No.12, pp. 861~919
COVER PICTURE
Structure of the fly peripheral neurons in the fly head. Flies have basic sensory organs including eyes for vision, antennae and maxillary palps for olfaction, and proboscis (magenta) for gustation which can be labelled with monoclonal antibody 22C10. The figure is a 3D reconstructed image with 30 slices of confocal sections with 3 μm interval. It shows that the proboscis is required for sensing attractive carboxylic acids such as glycolic acid, citric acid, and lactic acid (Shrestha and Lee, pp. 900-910).

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