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dc.contributor.author
Pedro, María del Pilar
dc.contributor.author
Vilcaes, Aldo Alejandro
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Tomatis, Vanesa Marisa
dc.contributor.author
Oliveira, Rafael Gustavo
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Gomez, Guillermo Alberto
dc.contributor.author
Daniotti, Jose Luis
dc.date.available
2015-06-04T19:01:59Z
dc.date.issued
2013-10
dc.identifier.citation
Pedro, María del Pilar; Vilcaes, Aldo Alejandro; Tomatis, Vanesa Marisa; Oliveira, Rafael Gustavo; Gomez, Guillermo Alberto; Daniotti, Jose Luis; 2-Bromopalmitate Reduces Protein Deacylation by Inhibition of Acyl-Protein Thioesterase Enzymatic Activities; Public Library Science; Plos One; 8; 10; 10-2013; e75232;
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/603
dc.description.abstract
S-acylation, the covalent attachment of palmitate and other fatty acids on cysteine residues, is a reversible post-translational modification that exerts diverse effects on protein functions. S-acylation is catalyzed by protein acyltransferases (PAT), while deacylation requires acyl-protein thioesterases (APT), with numerous inhibitors for these enzymes having already been developed and characterized. Among these inhibitors, the palmitate analog 2-brompalmitate (2-BP) is the most commonly used to inhibit palmitoylation in cells. Nevertheless, previous results from our laboratory have suggested that 2-BP could affect protein deacylation. Here, we further investigated in vivo and in vitro the effect of 2-BP on the acylation/deacylation protein machinery, with it being observed that 2-BP, in addition to inhibiting PAT activity in vivo, also perturbed the acylation cycle of GAP-43 at the level of depalmitoylation and consequently affected its kinetics of membrane association. Furthermore, 2-BP was able to inhibit in vitro the enzymatic activities of human APT1 and APT2, the only two thioesterases shown to mediate protein deacylation, through an uncompetitive mechanism of action. In fact, APT1 and APT2 hydrolyzed both the monomeric form as well as the micellar state of the substrate palmitoyl-CoA. On the basis of the obtained results, as APTs can mediate deacylation on membrane bound and unbound substrates, this suggests that the access of APTs to the membrane interface is not a necessary requisite for deacylation. Moreover, as the enzymatic activity of APTs was inhibited by 2-BP treatment, then the kinetics analysis of protein acylation using 2-BP should be carefully interpreted, as this drug also inhibits protein deacylation.
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application/pdf
dc.language.iso
eng
dc.publisher
Public Library Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
2-Bromopalmitate
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S-Acylation
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Thioesterases
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Enzymatic Activity
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Ciencias Naturales y Exactas
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Ciencias Biológicas
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Bioquímica y Biología Molecular (ídem 3.1.10)
dc.title
2-Bromopalmitate Reduces Protein Deacylation by Inhibition of Acyl-Protein Thioesterase Enzymatic Activities
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
8
dc.journal.number
10
dc.journal.pagination
e75232
dc.journal.pais
Estados Unidos
dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Pedro, María del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Centro de Investigaciones en Química Biológica de Cordoba (p); Argentina;
dc.description.fil
Fil: Vilcaes, Aldo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Centro de Investigaciones en Química Biológica de Cordoba (p); Argentina;
dc.description.fil
Fil: Tomatis, Vanesa Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Centro de Investigaciones en Química Biológica de Cordoba (p); Argentina; Queensland Brain Institute, The University of Queensland; Australia;
dc.description.fil
Fil: Oliveira, Rafael Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Centro de Investigaciones en Química Biológica de Cordoba (p); Argentina;
dc.description.fil
Fil: Gomez, Guillermo Alberto. Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane; Australia;
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Fil: Daniotti, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Centro de Investigaciones en Química Biológica de Cordoba (p); Argentina;
dc.journal.title
Plos One
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0075232
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