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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
Jul 31, 2022 Vol.45 No.7, pp. 435~512
COVER PICTURE
Mesenchymal stem cells (MSCs) are multipotent stem cells capable of differentiating into mesodermal lineages like adipogenic, osteogenic, and chondrogenic. Alcian blue-positive extracellular matrix secreted by chondrocytes in the lacuna confirmed the chondrogenic differentiation of MSCs (Bashyal et al., pp. 479-494).

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