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Int. J. Mol. Sci. 2018, 19(2), 368; https://doi.org/10.3390/ijms19020368

Microtubule-Actin Crosslinking Factor 1 and Plakins as Therapeutic Drug Targets

Department of Biological Sciences, Tennessee State University, 3500 John A. Merritt Blvd, Nashville, TN 37209, USA
Received: 11 December 2017 / Revised: 22 January 2018 / Accepted: 23 January 2018 / Published: 26 January 2018
(This article belongs to the Special Issue Microtubule-Targeting Agents)
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Abstract

Plakins are a family of seven cytoskeletal cross-linker proteins (microtubule-actin crosslinking factor 1 (MACF), bullous pemphigoid antigen (BPAG1) desmoplakin, envoplakin, periplakin, plectin, epiplakin) that network the three major filaments that comprise the cytoskeleton. Plakins have been found to be involved in disorders and diseases of the skin, heart, nervous system, and cancer that are attributed to autoimmune responses and genetic alterations of these macromolecules. Despite their role and involvement across a spectrum of several diseases, there are no current drugs or pharmacological agents that specifically target the members of this protein family. On the contrary, microtubules have traditionally been targeted by microtubule inhibiting agents, used for the treatment of diseases such as cancer, in spite of the deleterious toxicities associated with their clinical utility. The Research Collaboratory for Structural Bioinformatics (RCSB) was used here to identify therapeutic drugs targeting the plakin proteins, particularly the spectraplakins MACF1 and BPAG1, which contain microtubule-binding domains. RCSB analysis revealed that plakin proteins had 329 ligands, of which more than 50% were MACF1 and BPAG1 ligands and 10 were documented, clinically or experimentally, to have several therapeutic applications as anticancer, anti-inflammatory, and antibiotic agents. View Full-Text
Keywords: plakins; drug targets; cancer; cardiomyopathy; bullous pemhigoid plakins; drug targets; cancer; cardiomyopathy; bullous pemhigoid
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Quick, Q.A. Microtubule-Actin Crosslinking Factor 1 and Plakins as Therapeutic Drug Targets. Int. J. Mol. Sci. 2018, 19, 368.

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