The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery

A key step in autophagy is the conjugation by the E3-like Atg12-Atg5-Atg16 complex of the ubiquitin-like protein Atg8 to phosphatidylethanolamine on the autophagosomal membrane, a process known as lipida-tion. Previous work in yeast showed that recruitment of the E3-like complex to the preautophagos...

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Detalhes bibliográficos
Autores: Bueno-Arribas, Miranda, Cruz-Cuevas, Celia, Monforte-Martinez, Beatriz, Navas Hernández, María Ángeles, Escalante, Ricardo, Vincent, Olivier
Tipo de documento: artigo
Data de publicação:2025
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositório:Docta Complutense
Idioma:inglês
OAI Identifier:oai:docta.ucm.es:20.500.14352/116079
Acesso em linha:https://hdl.handle.net/20.500.14352/116079
Access Level:Acceso aberto
Palavra-chave:577.2
Autophagy
ATG17
ATG12
PKA
Reverse two-hybrid
Ciencias
24 Ciencias de la Vida
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oai_identifier_str oai:docta.ucm.es:20.500.14352/116079
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network_name_str España
repository_id_str
spelling The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation MachineryBueno-Arribas, MirandaCruz-Cuevas, CeliaMonforte-Martinez, BeatrizNavas Hernández, María ÁngelesEscalante, RicardoVincent, Olivier577.2AutophagyATG17ATG12PKAReverse two-hybridCiencias24 Ciencias de la VidaA key step in autophagy is the conjugation by the E3-like Atg12-Atg5-Atg16 complex of the ubiquitin-like protein Atg8 to phosphatidylethanolamine on the autophagosomal membrane, a process known as lipida-tion. Previous work in yeast showed that recruitment of the E3-like complex to the preautophagosomal structure is mediated by the interaction of Atg16 with the phosphatidylinositol 3-phosphate-binding protein Atg21, and by the association of Atg12 with the scaffold protein of the Atg1 kinase complex, Atg17. Here, we conducted a reverse two-hybrid screen to identify residues in Atg17 and Atg12 critical for Atg17-Atg12 binding, and used these data to generate a docking model of Atg12-Atg5-Atg16 with the Atg17 complex. In this model, a conserved alpha-helix in the N-terminal region of Atg12 binds to the convex side of crescent-shaped Atg17 and appears to form a four-helix bundle with the three helices of Atg17, similar to that described for the binding of Atg31 to Atg17. We further showed that, in agreement with previous work, Atg17-Atg12 and Atg21-Atg16 binding act cooperatively to mediate the recruitment of the E3-like complex, although our results show that alternative mechanisms are involved in this process. Finally, we found that phosphorylation of Atg12 by PKA prevents its interaction with Atg17, thus adding a new reg-ulatory layer in the control of autophagy by the PKA signaling pathway.ElsevierUniversidad Complutense de Madrid20252025-01-0120252025-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/116079reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PGC2018-093604-B-I00 FUNCION DE LOS SITIOS DE CONTACTO ENTRE MEMBRANAS Y EL TRAFICO DE LIPIDOS EN AUTOFAGIAopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1160792026-06-02T12:44:21Z
dc.title.none.fl_str_mv The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery
title The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery
spellingShingle The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery
Bueno-Arribas, Miranda
577.2
Autophagy
ATG17
ATG12
PKA
Reverse two-hybrid
Ciencias
24 Ciencias de la Vida
title_short The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery
title_full The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery
title_fullStr The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery
title_full_unstemmed The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery
title_sort The PKA Signaling Pathway Regulates the Association of the Autophagy Initiation Complex With the Lipidation Machinery
dc.creator.none.fl_str_mv Bueno-Arribas, Miranda
Cruz-Cuevas, Celia
Monforte-Martinez, Beatriz
Navas Hernández, María Ángeles
Escalante, Ricardo
Vincent, Olivier
author Bueno-Arribas, Miranda
author_facet Bueno-Arribas, Miranda
Cruz-Cuevas, Celia
Monforte-Martinez, Beatriz
Navas Hernández, María Ángeles
Escalante, Ricardo
Vincent, Olivier
author_role author
author2 Cruz-Cuevas, Celia
Monforte-Martinez, Beatriz
Navas Hernández, María Ángeles
Escalante, Ricardo
Vincent, Olivier
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 577.2
Autophagy
ATG17
ATG12
PKA
Reverse two-hybrid
Ciencias
24 Ciencias de la Vida
topic 577.2
Autophagy
ATG17
ATG12
PKA
Reverse two-hybrid
Ciencias
24 Ciencias de la Vida
description A key step in autophagy is the conjugation by the E3-like Atg12-Atg5-Atg16 complex of the ubiquitin-like protein Atg8 to phosphatidylethanolamine on the autophagosomal membrane, a process known as lipida-tion. Previous work in yeast showed that recruitment of the E3-like complex to the preautophagosomal structure is mediated by the interaction of Atg16 with the phosphatidylinositol 3-phosphate-binding protein Atg21, and by the association of Atg12 with the scaffold protein of the Atg1 kinase complex, Atg17. Here, we conducted a reverse two-hybrid screen to identify residues in Atg17 and Atg12 critical for Atg17-Atg12 binding, and used these data to generate a docking model of Atg12-Atg5-Atg16 with the Atg17 complex. In this model, a conserved alpha-helix in the N-terminal region of Atg12 binds to the convex side of crescent-shaped Atg17 and appears to form a four-helix bundle with the three helices of Atg17, similar to that described for the binding of Atg31 to Atg17. We further showed that, in agreement with previous work, Atg17-Atg12 and Atg21-Atg16 binding act cooperatively to mediate the recruitment of the E3-like complex, although our results show that alternative mechanisms are involved in this process. Finally, we found that phosphorylation of Atg12 by PKA prevents its interaction with Atg17, thus adding a new reg-ulatory layer in the control of autophagy by the PKA signaling pathway.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/116079
url https://hdl.handle.net/20.500.14352/116079
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PGC2018-093604-B-I00 FUNCION DE LOS SITIOS DE CONTACTO ENTRE MEMBRANAS Y EL TRAFICO DE LIPIDOS EN AUTOFAGIA
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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