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Calpain A modulates Toll responses by limited Cactus/IκB proteolysis

Calcium-dependent cysteine proteases of the calpain family are modulatory proteases that cleave their substrates in a limited manner. Among their substrates, calpains target vertebrate and invertebrate IκB proteins. Because proteolysis by calpains potentially generates novel protein functions, it is...

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Detalles Bibliográficos
Autores principales: Fontenele, Marcio, Lim, Bomyi, Oliveira, Danielle, Buffolo, Márcio, Perlman, David H., Schupbach, Trudi, Araujo, Helena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771957/
https://www.ncbi.nlm.nih.gov/pubmed/23864715
http://dx.doi.org/10.1091/mbc.E13-02-0113
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author Fontenele, Marcio
Lim, Bomyi
Oliveira, Danielle
Buffolo, Márcio
Perlman, David H.
Schupbach, Trudi
Araujo, Helena
author_facet Fontenele, Marcio
Lim, Bomyi
Oliveira, Danielle
Buffolo, Márcio
Perlman, David H.
Schupbach, Trudi
Araujo, Helena
author_sort Fontenele, Marcio
collection PubMed
description Calcium-dependent cysteine proteases of the calpain family are modulatory proteases that cleave their substrates in a limited manner. Among their substrates, calpains target vertebrate and invertebrate IκB proteins. Because proteolysis by calpains potentially generates novel protein functions, it is important to understand how this affects NFκB activity. We investigate the action of Calpain A (CalpA) on the Drosophila melanogaster IκB homologue Cactus in vivo. CalpA alters the absolute amounts of Cactus protein. Our data indicate, however, that CalpA uses additional mechanisms to regulate NFκB function. We provide evidence that CalpA interacts physically with Cactus, recognizing a Cactus pool that is not bound to Dorsal, a fly NFκB/Rel homologue. We show that proteolytic cleavage by CalpA generates Cactus fragments lacking an N-terminal region required for Toll responsiveness. These fragments are generated in vivo and display properties distinct from those of full-length Cactus. We propose that CalpA targets free Cactus, which is incorporated into and modulates Toll-responsive complexes in the embryo and immune system.
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spelling pubmed-37719572013-11-30 Calpain A modulates Toll responses by limited Cactus/IκB proteolysis Fontenele, Marcio Lim, Bomyi Oliveira, Danielle Buffolo, Márcio Perlman, David H. Schupbach, Trudi Araujo, Helena Mol Biol Cell Articles Calcium-dependent cysteine proteases of the calpain family are modulatory proteases that cleave their substrates in a limited manner. Among their substrates, calpains target vertebrate and invertebrate IκB proteins. Because proteolysis by calpains potentially generates novel protein functions, it is important to understand how this affects NFκB activity. We investigate the action of Calpain A (CalpA) on the Drosophila melanogaster IκB homologue Cactus in vivo. CalpA alters the absolute amounts of Cactus protein. Our data indicate, however, that CalpA uses additional mechanisms to regulate NFκB function. We provide evidence that CalpA interacts physically with Cactus, recognizing a Cactus pool that is not bound to Dorsal, a fly NFκB/Rel homologue. We show that proteolytic cleavage by CalpA generates Cactus fragments lacking an N-terminal region required for Toll responsiveness. These fragments are generated in vivo and display properties distinct from those of full-length Cactus. We propose that CalpA targets free Cactus, which is incorporated into and modulates Toll-responsive complexes in the embryo and immune system. The American Society for Cell Biology 2013-09-15 /pmc/articles/PMC3771957/ /pubmed/23864715 http://dx.doi.org/10.1091/mbc.E13-02-0113 Text en © 2013 Fontenele et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Fontenele, Marcio
Lim, Bomyi
Oliveira, Danielle
Buffolo, Márcio
Perlman, David H.
Schupbach, Trudi
Araujo, Helena
Calpain A modulates Toll responses by limited Cactus/IκB proteolysis
title Calpain A modulates Toll responses by limited Cactus/IκB proteolysis
title_full Calpain A modulates Toll responses by limited Cactus/IκB proteolysis
title_fullStr Calpain A modulates Toll responses by limited Cactus/IκB proteolysis
title_full_unstemmed Calpain A modulates Toll responses by limited Cactus/IκB proteolysis
title_short Calpain A modulates Toll responses by limited Cactus/IκB proteolysis
title_sort calpain a modulates toll responses by limited cactus/iκb proteolysis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771957/
https://www.ncbi.nlm.nih.gov/pubmed/23864715
http://dx.doi.org/10.1091/mbc.E13-02-0113
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