Zyxin: a mechanotransductor to regulate gene expression

Y.-X. Wang, D.-Y. Wang, Y.-C. Guo, J. Guo

Academy of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, China. Guoj@njucm.edu.cn

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• Pharmacology

OBJECTIVE: Cells answer to biochemical, electrical and mechanical signals in the environment, which regulate their behavior. Mechanical signals can propagate through mechanically stiff structures like focal adhesions (FAs). Zyxin, a LIM domain protein, is localized primarily at focal adhesion plaques. Growing evidence suggests that zyxin is a vital mechanotransductor to regulate the gene expression. In this review, we summarize the features of zyxin and the molecular mechanism of how zyxin participate in the cellular activity.

MATERIALS AND METHODS: An English-language literature search is based on a keyword-based query of multiple databases (MEDLINE, Embase) and bibliographies from identified publications. The references in the selected paper are also considered as an additional source of data. The search was last updated in April 2018; no limitations are applied.

RESULTS: Zyxin enhances actin polymerization with the aid of Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) proteins in response to mechanical tension, to perform its role in stress fibers (SFs) remodeling and repair. Zyxin can translocate from focal adhesions (FAs) to the nucleus responds to stretch, and regulate gene transcription by interaction with transcription factors like nuclear matrix protein 4 (NMP4). Misregulation of nuclear functions of zyxin appears to be associated with pathogenic effects and diseases, such as prostate cancer and non-small-cell lung cancer.

CONCLUSIONS: Zyxin is a crucial ingredient of the cellular mechanotransducing system and can modulate the gene expression. Given its clinical relevance, zyxin is also a promising target for the diagnosis and treatment of certain diseases. Understanding the role of zyxin in force sensing and gene expression regulating provides a compelling challenge for future biomechanics studies, and offers attractive evidence for zyxin as a potential diagnostic marker and therapeutic target for clinical diseases.

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