In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants

Autores
Gerez, Juan Atilio; Fuertes, Mariana; Tedesco, Lucas; Silberstein Cuña, Susana Iris; Sevlever, Gustavo; Paez-Pereda, Marcelo; Holsboer, Florian; Turjanski, Adrian; Arzt, Eduardo Simon
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
RSUME (RWD-containing SUMO Enhancer) is a small protein that increases SUMO conjugation to proteins. To date, four splice variants that codify three RSUME isoforms have been described, which differ in their C-terminal end. Comparing the structure of the RSUME isoforms we found that, in addition to the previously described RWD domain in the N-terminal, all these RSUME variants also contain an intermediate domain. Only the longest RSUME isoform presents a C-terminal domain that is absent in the others. Given these differences, we used the shortest and longest RSUME variants for comparative studies. We found that the C-terminal domain is dispensable for the SUMO-conjugation enhancer properties of RSUME. We also demonstrate that these two RSUME variants are equally induced by hypoxia. The NF-kB signaling pathway is inhibited, and the HIF-1 expression and HIF-1 activity are increased more efficiently by the longest RSUME. In addition, the mRNA levels of these isoforms differ in human glioma samples; while the shortest RSUME isoform is expressed in all the tumors analyzed, the longest variant is expressed in most but not all of them. The results presented here show a degree of redundancy of the RSUME variants on the SUMO pathway. However, the increased inhibition conferred by RSUME267 over the NF-kB signaling pathway, the increased activation over the HIF-1 pathway and the different expression of the RSUME isoforms suggest specific roles for each RSUME isoform which may be relevant in certain types of brain tumors that express RSUME, like human pituitary adenomas and gliomas.
Fil: Gerez, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;
Fil: Fuertes, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;
Fil: Tedesco, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;
Fil: Silberstein Cuña, Susana Iris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiologia, Biologia Molecular y Celular. Laboratorio de Fisiologia y Biologia Molecular; Argentina;
Fil: Sevlever, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;
Fil: Paez-Pereda, Marcelo. Max Planck Institute of Psychiatry; Alemania;
Fil: Holsboer, Florian. Max Planck Institute of Psychiatry; Alemania;
Fil: Turjanski, Adrian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; Argentina;
Fil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto P; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiologia, Biologia Molecular y Celular. Laboratorio de Fisiologia y Biologia Molecular; Argentina;
Materia
NFkB
SUMOYLATION
SUMO
HIF-1
NFKB
PITUITARY ADENOMA
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:11336/689
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/689
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variantsGerez, Juan AtilioFuertes, MarianaTedesco, LucasSilberstein Cuña, Susana IrisSevlever, GustavoPaez-Pereda, MarceloHolsboer, FlorianTurjanski, AdrianArzt, Eduardo SimonNFkBSUMOYLATIONSUMOHIF-1NFKBPITUITARY ADENOMAhttps://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1RSUME (RWD-containing SUMO Enhancer) is a small protein that increases SUMO conjugation to proteins. To date, four splice variants that codify three RSUME isoforms have been described, which differ in their C-terminal end. Comparing the structure of the RSUME isoforms we found that, in addition to the previously described RWD domain in the N-terminal, all these RSUME variants also contain an intermediate domain. Only the longest RSUME isoform presents a C-terminal domain that is absent in the others. Given these differences, we used the shortest and longest RSUME variants for comparative studies. We found that the C-terminal domain is dispensable for the SUMO-conjugation enhancer properties of RSUME. We also demonstrate that these two RSUME variants are equally induced by hypoxia. The NF-kB signaling pathway is inhibited, and the HIF-1 expression and HIF-1 activity are increased more efficiently by the longest RSUME. In addition, the mRNA levels of these isoforms differ in human glioma samples; while the shortest RSUME isoform is expressed in all the tumors analyzed, the longest variant is expressed in most but not all of them. The results presented here show a degree of redundancy of the RSUME variants on the SUMO pathway. However, the increased inhibition conferred by RSUME267 over the NF-kB signaling pathway, the increased activation over the HIF-1 pathway and the different expression of the RSUME isoforms suggest specific roles for each RSUME isoform which may be relevant in certain types of brain tumors that express RSUME, like human pituitary adenomas and gliomas.Fil: Gerez, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;Fil: Fuertes, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;Fil: Tedesco, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;Fil: Silberstein Cuña, Susana Iris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiologia, Biologia Molecular y Celular. Laboratorio de Fisiologia y Biologia Molecular; Argentina;Fil: Sevlever, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;Fil: Paez-Pereda, Marcelo. Max Planck Institute of Psychiatry; Alemania;Fil: Holsboer, Florian. Max Planck Institute of Psychiatry; Alemania;Fil: Turjanski, Adrian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; Argentina;Fil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto P; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiologia, Biologia Molecular y Celular. Laboratorio de Fisiologia y Biologia Molecular; Argentina;Public Library Science2013-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/689Gerez, Juan Atilio; Fuertes, Mariana; Tedesco, Lucas; Silberstein Cuña, Susana Iris; Sevlever, Gustavo; et al.;In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants; Public Library Science; Plos One; 8; 2-2013; 1-131932-6203enginfo:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0057795info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0057795info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:43:24Zoai:ri.conicet.gov.ar:11336/689instacron: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 15:43:25.22CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants
title In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants
spellingShingle In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants
Gerez, Juan Atilio
NFkB
SUMOYLATION
SUMO
HIF-1
NFKB
PITUITARY ADENOMA
title_short In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants
title_full In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants
title_fullStr In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants
title_full_unstemmed In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants
title_sort In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants
dc.creator.none.fl_str_mv Gerez, Juan Atilio
Fuertes, Mariana
Tedesco, Lucas
Silberstein Cuña, Susana Iris
Sevlever, Gustavo
Paez-Pereda, Marcelo
Holsboer, Florian
Turjanski, Adrian
Arzt, Eduardo Simon
author Gerez, Juan Atilio
author_facet Gerez, Juan Atilio
Fuertes, Mariana
Tedesco, Lucas
Silberstein Cuña, Susana Iris
Sevlever, Gustavo
Paez-Pereda, Marcelo
Holsboer, Florian
Turjanski, Adrian
Arzt, Eduardo Simon
author_role author
author2 Fuertes, Mariana
Tedesco, Lucas
Silberstein Cuña, Susana Iris
Sevlever, Gustavo
Paez-Pereda, Marcelo
Holsboer, Florian
Turjanski, Adrian
Arzt, Eduardo Simon
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NFkB
SUMOYLATION
SUMO
HIF-1
NFKB
PITUITARY ADENOMA
topic NFkB
SUMOYLATION
SUMO
HIF-1
NFKB
PITUITARY ADENOMA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
dc.description.none.fl_txt_mv RSUME (RWD-containing SUMO Enhancer) is a small protein that increases SUMO conjugation to proteins. To date, four splice variants that codify three RSUME isoforms have been described, which differ in their C-terminal end. Comparing the structure of the RSUME isoforms we found that, in addition to the previously described RWD domain in the N-terminal, all these RSUME variants also contain an intermediate domain. Only the longest RSUME isoform presents a C-terminal domain that is absent in the others. Given these differences, we used the shortest and longest RSUME variants for comparative studies. We found that the C-terminal domain is dispensable for the SUMO-conjugation enhancer properties of RSUME. We also demonstrate that these two RSUME variants are equally induced by hypoxia. The NF-kB signaling pathway is inhibited, and the HIF-1 expression and HIF-1 activity are increased more efficiently by the longest RSUME. In addition, the mRNA levels of these isoforms differ in human glioma samples; while the shortest RSUME isoform is expressed in all the tumors analyzed, the longest variant is expressed in most but not all of them. The results presented here show a degree of redundancy of the RSUME variants on the SUMO pathway. However, the increased inhibition conferred by RSUME267 over the NF-kB signaling pathway, the increased activation over the HIF-1 pathway and the different expression of the RSUME isoforms suggest specific roles for each RSUME isoform which may be relevant in certain types of brain tumors that express RSUME, like human pituitary adenomas and gliomas.
Fil: Gerez, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;
Fil: Fuertes, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;
Fil: Tedesco, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;
Fil: Silberstein Cuña, Susana Iris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiologia, Biologia Molecular y Celular. Laboratorio de Fisiologia y Biologia Molecular; Argentina;
Fil: Sevlever, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto Partner Sociedad Max Planck; Argentina;
Fil: Paez-Pereda, Marcelo. Max Planck Institute of Psychiatry; Alemania;
Fil: Holsboer, Florian. Max Planck Institute of Psychiatry; Alemania;
Fil: Turjanski, Adrian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; Argentina;
Fil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación en Biomedicina de Buenos Aores - CONICET -Instituto P; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiologia, Biologia Molecular y Celular. Laboratorio de Fisiologia y Biologia Molecular; Argentina;
description RSUME (RWD-containing SUMO Enhancer) is a small protein that increases SUMO conjugation to proteins. To date, four splice variants that codify three RSUME isoforms have been described, which differ in their C-terminal end. Comparing the structure of the RSUME isoforms we found that, in addition to the previously described RWD domain in the N-terminal, all these RSUME variants also contain an intermediate domain. Only the longest RSUME isoform presents a C-terminal domain that is absent in the others. Given these differences, we used the shortest and longest RSUME variants for comparative studies. We found that the C-terminal domain is dispensable for the SUMO-conjugation enhancer properties of RSUME. We also demonstrate that these two RSUME variants are equally induced by hypoxia. The NF-kB signaling pathway is inhibited, and the HIF-1 expression and HIF-1 activity are increased more efficiently by the longest RSUME. In addition, the mRNA levels of these isoforms differ in human glioma samples; while the shortest RSUME isoform is expressed in all the tumors analyzed, the longest variant is expressed in most but not all of them. The results presented here show a degree of redundancy of the RSUME variants on the SUMO pathway. However, the increased inhibition conferred by RSUME267 over the NF-kB signaling pathway, the increased activation over the HIF-1 pathway and the different expression of the RSUME isoforms suggest specific roles for each RSUME isoform which may be relevant in certain types of brain tumors that express RSUME, like human pituitary adenomas and gliomas.
publishDate 2013
dc.date.none.fl_str_mv 2013-02
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/11336/689
Gerez, Juan Atilio; Fuertes, Mariana; Tedesco, Lucas; Silberstein Cuña, Susana Iris; Sevlever, Gustavo; et al.;In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants; Public Library Science; Plos One; 8; 2-2013; 1-13
1932-6203
url http://hdl.handle.net/11336/689
identifier_str_mv Gerez, Juan Atilio; Fuertes, Mariana; Tedesco, Lucas; Silberstein Cuña, Susana Iris; Sevlever, Gustavo; et al.;In silico structural and functional characterization of the RSUME splice variants Short title: RSUME splice variants; Public Library Science; Plos One; 8; 2-2013; 1-13
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0057795
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0057795
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.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
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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