Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus

Autores
Lausero, Luciano Nicolás; Loos, Julia Alexandra; Gomez Bardich, Nazareno; Cumino, Andrea Carina
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Echinococcus granulosus is the causative agent of human cystic echinococcosis, a zoonotic infection endemic in many areas throughout the world. Once an individual is infected, this cestode forms metacestodes, which grow in host organs, thus, causing the disease. Identification of new drug targets is urgently required given the toxicity and poor efficacy of available drugs. The protein SQSTM1/p62 plays an important role in selective autophagy in different cellular systems, under stress situations as drug exposure, hypoxia and starvation. In this work we identified, re-named, and deposited in GenBank a putative orthologous gene of sqtsm1/p62 in E. granulosus (ID2837631), based on BLAST searches against the parasite genome (E-value cutoff 1e-25), the occurrence of conserved structural domains, and the transcriptional induction and in situ immunodetection under conditions of autophagy activation. The full-length open reading frame of Eg-p62 predicts a protein with 35% identity to the human ortholog (AAH01874 and Q13501), with a conserved domain structure containing the domains PB1 (homodimerization site with characteristic charged residues), ZZ (conserved amino-acids involved in autophagy regulation), IDR (binding sites for Raptor, LC3 and KEAP1) and UBA with ubiquitinated protein binding sites, allowing self-degradation and proteolysis of other ubiquitin-tagged proteins. By in totoimmune-localization assays and using autophagy-inducing-drugs such as rapamycin and hydroxychloroquine, we observed huge spherical aggregates (0.5-3 μm) around the nucleus in metacestodes and protoscoleces, and a positive signal in calcareous corpuscles and protonephridia. Inaddition, by qPCR analysis, we found that these drugs induced a two-threefold increase in Egsqstm1/p62 mRNA levels compared to untreated parasites. Here, we discuss the effects of Eg-p62 on the proteostatic status and aggrephagy in cestodes.
Fil: Lausero, Luciano Nicolás. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Fil: Gomez Bardich, Nazareno. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
XXVII Congreso de la Federación Latinoamericana de Parasitología; XII Congreso de la Sociedad Argentina de Protozoología
Buenos Aires
Argentina
Sociedad Argentina de Protozoología
Materia
ECHINOCOCCUS
AUTOPHAGY
p62
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/261160
Acceder
id CONICETDig_057579fa4ac06589ddb0927adf8ac270
oai_identifier_str oai:ri.conicet.gov.ar:11336/261160
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosusLausero, Luciano NicolásLoos, Julia AlexandraGomez Bardich, NazarenoCumino, Andrea CarinaECHINOCOCCUSAUTOPHAGYp62https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Echinococcus granulosus is the causative agent of human cystic echinococcosis, a zoonotic infection endemic in many areas throughout the world. Once an individual is infected, this cestode forms metacestodes, which grow in host organs, thus, causing the disease. Identification of new drug targets is urgently required given the toxicity and poor efficacy of available drugs. The protein SQSTM1/p62 plays an important role in selective autophagy in different cellular systems, under stress situations as drug exposure, hypoxia and starvation. In this work we identified, re-named, and deposited in GenBank a putative orthologous gene of sqtsm1/p62 in E. granulosus (ID2837631), based on BLAST searches against the parasite genome (E-value cutoff 1e-25), the occurrence of conserved structural domains, and the transcriptional induction and in situ immunodetection under conditions of autophagy activation. The full-length open reading frame of Eg-p62 predicts a protein with 35% identity to the human ortholog (AAH01874 and Q13501), with a conserved domain structure containing the domains PB1 (homodimerization site with characteristic charged residues), ZZ (conserved amino-acids involved in autophagy regulation), IDR (binding sites for Raptor, LC3 and KEAP1) and UBA with ubiquitinated protein binding sites, allowing self-degradation and proteolysis of other ubiquitin-tagged proteins. By in totoimmune-localization assays and using autophagy-inducing-drugs such as rapamycin and hydroxychloroquine, we observed huge spherical aggregates (0.5-3 μm) around the nucleus in metacestodes and protoscoleces, and a positive signal in calcareous corpuscles and protonephridia. Inaddition, by qPCR analysis, we found that these drugs induced a two-threefold increase in Egsqstm1/p62 mRNA levels compared to untreated parasites. Here, we discuss the effects of Eg-p62 on the proteostatic status and aggrephagy in cestodes.Fil: Lausero, Luciano Nicolás. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Gomez Bardich, Nazareno. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaXXVII Congreso de la Federación Latinoamericana de Parasitología; XII Congreso de la Sociedad Argentina de ProtozoologíaBuenos AiresArgentinaSociedad Argentina de ProtozoologíaSociedad Argentina de Protozoologia2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/261160Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus; XXVII Congreso de la Federación Latinoamericana de Parasitología; XII Congreso de la Sociedad Argentina de Protozoología; Buenos Aires; Argentina; 2024; 100-1002953-5751CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://protozoologia.org.ar/revista-parasitus/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:49:41Zoai:ri.conicet.gov.ar:11336/261160instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:49:41.925CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus
title Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus
spellingShingle Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus
Lausero, Luciano Nicolás
ECHINOCOCCUS
AUTOPHAGY
p62
title_short Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus
title_full Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus
title_fullStr Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus
title_full_unstemmed Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus
title_sort Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus
dc.creator.none.fl_str_mv Lausero, Luciano Nicolás
Loos, Julia Alexandra
Gomez Bardich, Nazareno
Cumino, Andrea Carina
author Lausero, Luciano Nicolás
author_facet Lausero, Luciano Nicolás
Loos, Julia Alexandra
Gomez Bardich, Nazareno
Cumino, Andrea Carina
author_role author
author2 Loos, Julia Alexandra
Gomez Bardich, Nazareno
Cumino, Andrea Carina
author2_role author
author
author
dc.subject.none.fl_str_mv ECHINOCOCCUS
AUTOPHAGY
p62
topic ECHINOCOCCUS
AUTOPHAGY
p62
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Echinococcus granulosus is the causative agent of human cystic echinococcosis, a zoonotic infection endemic in many areas throughout the world. Once an individual is infected, this cestode forms metacestodes, which grow in host organs, thus, causing the disease. Identification of new drug targets is urgently required given the toxicity and poor efficacy of available drugs. The protein SQSTM1/p62 plays an important role in selective autophagy in different cellular systems, under stress situations as drug exposure, hypoxia and starvation. In this work we identified, re-named, and deposited in GenBank a putative orthologous gene of sqtsm1/p62 in E. granulosus (ID2837631), based on BLAST searches against the parasite genome (E-value cutoff 1e-25), the occurrence of conserved structural domains, and the transcriptional induction and in situ immunodetection under conditions of autophagy activation. The full-length open reading frame of Eg-p62 predicts a protein with 35% identity to the human ortholog (AAH01874 and Q13501), with a conserved domain structure containing the domains PB1 (homodimerization site with characteristic charged residues), ZZ (conserved amino-acids involved in autophagy regulation), IDR (binding sites for Raptor, LC3 and KEAP1) and UBA with ubiquitinated protein binding sites, allowing self-degradation and proteolysis of other ubiquitin-tagged proteins. By in totoimmune-localization assays and using autophagy-inducing-drugs such as rapamycin and hydroxychloroquine, we observed huge spherical aggregates (0.5-3 μm) around the nucleus in metacestodes and protoscoleces, and a positive signal in calcareous corpuscles and protonephridia. Inaddition, by qPCR analysis, we found that these drugs induced a two-threefold increase in Egsqstm1/p62 mRNA levels compared to untreated parasites. Here, we discuss the effects of Eg-p62 on the proteostatic status and aggrephagy in cestodes.
Fil: Lausero, Luciano Nicolás. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Fil: Gomez Bardich, Nazareno. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
XXVII Congreso de la Federación Latinoamericana de Parasitología; XII Congreso de la Sociedad Argentina de Protozoología
Buenos Aires
Argentina
Sociedad Argentina de Protozoología
description Echinococcus granulosus is the causative agent of human cystic echinococcosis, a zoonotic infection endemic in many areas throughout the world. Once an individual is infected, this cestode forms metacestodes, which grow in host organs, thus, causing the disease. Identification of new drug targets is urgently required given the toxicity and poor efficacy of available drugs. The protein SQSTM1/p62 plays an important role in selective autophagy in different cellular systems, under stress situations as drug exposure, hypoxia and starvation. In this work we identified, re-named, and deposited in GenBank a putative orthologous gene of sqtsm1/p62 in E. granulosus (ID2837631), based on BLAST searches against the parasite genome (E-value cutoff 1e-25), the occurrence of conserved structural domains, and the transcriptional induction and in situ immunodetection under conditions of autophagy activation. The full-length open reading frame of Eg-p62 predicts a protein with 35% identity to the human ortholog (AAH01874 and Q13501), with a conserved domain structure containing the domains PB1 (homodimerization site with characteristic charged residues), ZZ (conserved amino-acids involved in autophagy regulation), IDR (binding sites for Raptor, LC3 and KEAP1) and UBA with ubiquitinated protein binding sites, allowing self-degradation and proteolysis of other ubiquitin-tagged proteins. By in totoimmune-localization assays and using autophagy-inducing-drugs such as rapamycin and hydroxychloroquine, we observed huge spherical aggregates (0.5-3 μm) around the nucleus in metacestodes and protoscoleces, and a positive signal in calcareous corpuscles and protonephridia. Inaddition, by qPCR analysis, we found that these drugs induced a two-threefold increase in Egsqstm1/p62 mRNA levels compared to untreated parasites. Here, we discuss the effects of Eg-p62 on the proteostatic status and aggrephagy in cestodes.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/261160
Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus; XXVII Congreso de la Federación Latinoamericana de Parasitología; XII Congreso de la Sociedad Argentina de Protozoología; Buenos Aires; Argentina; 2024; 100-100
2953-5751
CONICET Digital
CONICET
url http://hdl.handle.net/11336/261160
identifier_str_mv Identification and functional characterization of SQSTM1/p62 and its importance in the autophagy process in Echinococcus granulosus; XXVII Congreso de la Federación Latinoamericana de Parasitología; XII Congreso de la Sociedad Argentina de Protozoología; Buenos Aires; Argentina; 2024; 100-100
2953-5751
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://protozoologia.org.ar/revista-parasitus/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Protozoologia
publisher.none.fl_str_mv Sociedad Argentina de Protozoologia
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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