Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target

Gabrielsen, M. , Schuldt, M., Munro, J., Borucka, D., Cameron, J., Baugh, M., Mleczak, A., Lilla, S., Morrice, N. and Olson, M.F. (2013) Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. Cell Communication and Signaling, 11(58), (doi: 10.1186/1478-811X-11-58)

Abstract

<p>Background: Cucurbitacins are a class of triterpenoid natural compounds with potent bioactivities that led to their use as traditional remedies, and which continue to attract considerable attention as chemical biology tools and potential therapeutics. One obvious target is the actin-cytoskeleton; treatment with cucurbitacins results in cytoskeletal rearrangements that impact upon motility and cell morphology.</p> <p>Findings: Cucurbitacin reacted with protein cysteine thiols as well as dithiothreitol, and we propose that the cucurbitacin mechanism of action is through broad protein thiol modifications that could result in inhibition of numerous protein targets. An example of such a target protein is Cofilin1, whose filamentous actin severing activity is inhibited by cucurbitacin conjugation.</p> <p>Conclusions: The implications of these results are that cucurbitacins are unlikely to be improved for selectivity by medicinal chemistry and that their use as chemical biology probes to analyse the role of specific signalling pathways should be undertaken with caution.</p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Munro, Dr June and Lilla, Dr Sergio and Gabrielsen, Dr Mads and Baugh, Dr Mark and Olson, Professor Michael and Morrice, Dr Nicholas
• Authors: Gabrielsen, M., Schuldt, M., Munro, J., Borucka, D., Cameron, J., Baugh, M., Mleczak, A., Lilla, S., Morrice, N., and Olson, M.F.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Communication and Signaling
• Publisher: BioMed Central
• ISSN: 1478-811X
• Published Online: 14 August 2013
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First published in Cell Communication and Signaling 11:58
• Publisher Policy: Reproduced under a Creative Commons License