The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling

Autores
Zgajnar, Nadia Romina; Daneri Becerra, Cristina del Rosario; Cauerff, Ana Albina; Galigniana, Mario Daniel
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The immunophilin FKBP51 forms heterocomplexes with molecular chaperones, protein-kinases, protein-phosphatases, autophagy-related factors, and transcription factors. Like most scaffold proteins, FKBP51 can use a simple tethering mechanism to favor the efficiency of interactions with partner molecules, but it can also exert more complex allosteric controls over client factors, the immunophilin itself being a putative regulation target. One of the simplest strategies for regulating pathways and subcellular localization of proteins is phosphorylation. In this study, it is shown that scaffold immunophilin FKBP51 is resolved by resolutive electrophoresis in various phosphorylated isoforms. This was evidenced by their reactivity with specific anti-phosphoamino acid antibodies and their fade-out by treatment with alkaline phosphatase. Interestingly, stress situations such as exposure to oxidants or in vivo fasting favors FKBP51 translocation from mitochondria to the nucleus. While fasting involves phosphothreonine residues, oxidative stress involves tyrosine residues. Molecular modeling predicts the existence of potential targets located at the FK1 domain of the immunophilin. Thus, oxidative stress favors FKBP51 dephosphorylation and protein degradation by the proteasome, whereas FK506 binding protects the persistence of the post-translational modification in tyrosine, leading to FKBP51 stability under oxidative conditions. Therefore, FKBP51 is revealed as a phosphoprotein that undergoes differential phosphorylations according to the stimulus.
Fil: Zgajnar, Nadia Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Daneri Becerra, Cristina del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Cauerff, Ana Albina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
FKBP51
IMMUNOPHILIN
NUCLEAR-MITOCHONDRIAL SHUTTLING
PHOSPHOAMINO ACID
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/224463
Acceder
id CONICETDig_40b7a92fb9d72949fbbba5c35cb39677
oai_identifier_str oai:ri.conicet.gov.ar:11336/224463
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear ShuttlingZgajnar, Nadia RominaDaneri Becerra, Cristina del RosarioCauerff, Ana AlbinaGaligniana, Mario DanielFKBP51IMMUNOPHILINNUCLEAR-MITOCHONDRIAL SHUTTLINGPHOSPHOAMINO ACIDhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The immunophilin FKBP51 forms heterocomplexes with molecular chaperones, protein-kinases, protein-phosphatases, autophagy-related factors, and transcription factors. Like most scaffold proteins, FKBP51 can use a simple tethering mechanism to favor the efficiency of interactions with partner molecules, but it can also exert more complex allosteric controls over client factors, the immunophilin itself being a putative regulation target. One of the simplest strategies for regulating pathways and subcellular localization of proteins is phosphorylation. In this study, it is shown that scaffold immunophilin FKBP51 is resolved by resolutive electrophoresis in various phosphorylated isoforms. This was evidenced by their reactivity with specific anti-phosphoamino acid antibodies and their fade-out by treatment with alkaline phosphatase. Interestingly, stress situations such as exposure to oxidants or in vivo fasting favors FKBP51 translocation from mitochondria to the nucleus. While fasting involves phosphothreonine residues, oxidative stress involves tyrosine residues. Molecular modeling predicts the existence of potential targets located at the FK1 domain of the immunophilin. Thus, oxidative stress favors FKBP51 dephosphorylation and protein degradation by the proteasome, whereas FK506 binding protects the persistence of the post-translational modification in tyrosine, leading to FKBP51 stability under oxidative conditions. Therefore, FKBP51 is revealed as a phosphoprotein that undergoes differential phosphorylations according to the stimulus.Fil: Zgajnar, Nadia Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Daneri Becerra, Cristina del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cauerff, Ana Albina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaMDPI2022-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/224463Zgajnar, Nadia Romina; Daneri Becerra, Cristina del Rosario; Cauerff, Ana Albina; Galigniana, Mario Daniel; The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling; MDPI; Cells; 11; 23; 12-2022; 1-132073-44092073-4409CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/cells11233771info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:14Zoai:ri.conicet.gov.ar:11336/224463instacron: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:34982025-09-29 09:36:14.356CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling
title The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling
spellingShingle The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling
Zgajnar, Nadia Romina
FKBP51
IMMUNOPHILIN
NUCLEAR-MITOCHONDRIAL SHUTTLING
PHOSPHOAMINO ACID
title_short The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling
title_full The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling
title_fullStr The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling
title_full_unstemmed The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling
title_sort The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling
dc.creator.none.fl_str_mv Zgajnar, Nadia Romina
Daneri Becerra, Cristina del Rosario
Cauerff, Ana Albina
Galigniana, Mario Daniel
author Zgajnar, Nadia Romina
author_facet Zgajnar, Nadia Romina
Daneri Becerra, Cristina del Rosario
Cauerff, Ana Albina
Galigniana, Mario Daniel
author_role author
author2 Daneri Becerra, Cristina del Rosario
Cauerff, Ana Albina
Galigniana, Mario Daniel
author2_role author
author
author
dc.subject.none.fl_str_mv FKBP51
IMMUNOPHILIN
NUCLEAR-MITOCHONDRIAL SHUTTLING
PHOSPHOAMINO ACID
topic FKBP51
IMMUNOPHILIN
NUCLEAR-MITOCHONDRIAL SHUTTLING
PHOSPHOAMINO ACID
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The immunophilin FKBP51 forms heterocomplexes with molecular chaperones, protein-kinases, protein-phosphatases, autophagy-related factors, and transcription factors. Like most scaffold proteins, FKBP51 can use a simple tethering mechanism to favor the efficiency of interactions with partner molecules, but it can also exert more complex allosteric controls over client factors, the immunophilin itself being a putative regulation target. One of the simplest strategies for regulating pathways and subcellular localization of proteins is phosphorylation. In this study, it is shown that scaffold immunophilin FKBP51 is resolved by resolutive electrophoresis in various phosphorylated isoforms. This was evidenced by their reactivity with specific anti-phosphoamino acid antibodies and their fade-out by treatment with alkaline phosphatase. Interestingly, stress situations such as exposure to oxidants or in vivo fasting favors FKBP51 translocation from mitochondria to the nucleus. While fasting involves phosphothreonine residues, oxidative stress involves tyrosine residues. Molecular modeling predicts the existence of potential targets located at the FK1 domain of the immunophilin. Thus, oxidative stress favors FKBP51 dephosphorylation and protein degradation by the proteasome, whereas FK506 binding protects the persistence of the post-translational modification in tyrosine, leading to FKBP51 stability under oxidative conditions. Therefore, FKBP51 is revealed as a phosphoprotein that undergoes differential phosphorylations according to the stimulus.
Fil: Zgajnar, Nadia Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Daneri Becerra, Cristina del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Cauerff, Ana Albina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description The immunophilin FKBP51 forms heterocomplexes with molecular chaperones, protein-kinases, protein-phosphatases, autophagy-related factors, and transcription factors. Like most scaffold proteins, FKBP51 can use a simple tethering mechanism to favor the efficiency of interactions with partner molecules, but it can also exert more complex allosteric controls over client factors, the immunophilin itself being a putative regulation target. One of the simplest strategies for regulating pathways and subcellular localization of proteins is phosphorylation. In this study, it is shown that scaffold immunophilin FKBP51 is resolved by resolutive electrophoresis in various phosphorylated isoforms. This was evidenced by their reactivity with specific anti-phosphoamino acid antibodies and their fade-out by treatment with alkaline phosphatase. Interestingly, stress situations such as exposure to oxidants or in vivo fasting favors FKBP51 translocation from mitochondria to the nucleus. While fasting involves phosphothreonine residues, oxidative stress involves tyrosine residues. Molecular modeling predicts the existence of potential targets located at the FK1 domain of the immunophilin. Thus, oxidative stress favors FKBP51 dephosphorylation and protein degradation by the proteasome, whereas FK506 binding protects the persistence of the post-translational modification in tyrosine, leading to FKBP51 stability under oxidative conditions. Therefore, FKBP51 is revealed as a phosphoprotein that undergoes differential phosphorylations according to the stimulus.
publishDate 2022
dc.date.none.fl_str_mv 2022-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/224463
Zgajnar, Nadia Romina; Daneri Becerra, Cristina del Rosario; Cauerff, Ana Albina; Galigniana, Mario Daniel; The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling; MDPI; Cells; 11; 23; 12-2022; 1-13
2073-4409
2073-4409
CONICET Digital
CONICET
url http://hdl.handle.net/11336/224463
identifier_str_mv Zgajnar, Nadia Romina; Daneri Becerra, Cristina del Rosario; Cauerff, Ana Albina; Galigniana, Mario Daniel; The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling; MDPI; Cells; 11; 23; 12-2022; 1-13
2073-4409
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/cells11233771
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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
_version_ 1844613134583595008
score 13.070432

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