Key result
LIM kinases control microtubule dynamics independently of actin microfilaments, and recently developed LIM kinase inhibitors show potential therapeutic effects in animal models of various diseases.
This review highlights the expanded role of LIM kinases in microtubule dynamics and summarizes the development of new LIM kinase inhibitors for potential therapeutic use.
LIM kinase inhibitors merit human trials; leaves open clinical translation beyond animal models.
// Chloé Prunier 1,2 , Renaud Prudent 3 , Reuben Kapur 4 , Karin Sadoul 1 and Laurence Lafanechère 1 1 Institute for Advanced Biosciences, INSERM, CNRS UMR, Université Grenoble Alpes, Grenoble, France 2 Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands 3 Cellipse SAS, MINATEC-BHT A441, Grenoble Cedex, France 4 Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA Correspondence to: Laurence Lafanechère, email: // Keywords : LIM kinases, cytoskeleton, microtubules, inhibitors Received : January 28, 2017 Accepted : March 10, 2017 Published : April 09, 2017 Abstract LIM kinases are common downstream effectors of several signalization pathways and function as a signaling node that controls cytoskeleton dynamics through the phosphorylation of the cofilin family proteins. These last 10 years, several reports indicate that the functions of LIM kinases are more extended than initially described and, specifically, that LIM kinases also control microtubule dynamics, independently of their regulation of actin microfilament. In this review we analyze the data supporting these conclusions and the possible mechanisms that could be involved in the control of microtubules by LIM kinases. The demonstration that LIM kinases also control microtubule dynamics has pointed to new therapeutic opportunities. Consistently, several new LIM kinase inhibitors have been recently developed. We provide a comprehensive comparison of these inhibitors, of their chemical structure, their specificity, their cellular effects as well as their effects in animal models of various diseases including cancer.
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Prunier et al. (2017) reported a review. LIM kinase inhibitors was evaluated. LIM kinases control microtubule dynamics independently of actin microfilaments, and recently developed LIM kinase inhibitors show potential therapeutic effects in animal models of various diseases.
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