The Use of Withaferin A to Study Intermediate Filaments

Methods in Enzymology
Royce Mohan, Paola Bargagna-Mohan

Abstract

Withaferin A (WFA), initially identified as a compound that inhibits experimental angiogenesis, has been shown to bind to soluble vimentin (sVim) and other type III intermediate filament (IF) proteins. We review WFA's dose-related activities (Section 1), examining nanomolar concentrations effects on sVim in cell proliferation and submicromolar effects on lamellipodia and focal adhesion formation. WFA effects on polymeric IFs are especially interesting to the study of cell migration and invasion that depend on IF mechanical contractile properties. WFA interferes with NF-κB signaling, though this anti-inflammatory mechanism may occur via perturbation of sVim-protein complexes, and possibly also via targeting IκB kinase β directly. However, micromolar concentrations that induce vimentin cleavage to promote apoptosis may increasingly show off-target effects via targeting other IFs (neurofilaments and keratin) and non-IFs (tubulin, heat-shock proteins, proteasome). Thus, in Section 2, we describe our studies combining cell cultures with animal models of injury to validate relevant type III IF-targeting mechanisms of WFA. In Section 3, we illuminate from investigating myofibroblast differentiation how sVim phosphorylation may govern ...Continue Reading

Citations

May 11, 2017·Journal of Neuroscience Research·Paola Bargagna-MohanRoyce Mohan
Jul 8, 2020·International Journal of Molecular Sciences·Irene RamosDolores Pérez-Sala
Sep 15, 2019·Nature Communications·Sofia DuarteDolores Pérez-Sala
Nov 17, 2019·International Journal of Molecular Sciences·Rinku DuttaSubhra Mohapatra
Jul 28, 2020·Redox Biology·Álvaro Viedma-PoyatosDolores Pérez-Sala
Nov 28, 2020·Cell Host & Microbe·Mirko CorteseRalf Bartenschlager

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