In Silico Structural and Functional Characterization of the RSUME Splice Variants

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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 t...

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Autores principales:	Gerez, J., Fuertes, M., Tedesco, L., Silberstein, S., Sevlever, G., Paez-Pereda, M., Holsboer, F., Turjanski, A.G., Arzt, E.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2013
Materias:	hypoxia inducible factor 1 immunoglobulin enhancer binding protein messenger RNA protein variant regulator protein RWD containing SUMO enhancer protein SUMO protein unclassified drug isoprotein RSUME protein, human SUMO 1 protein transcription factor article brain cancer carboxy terminal sequence computer model controlled study gene expression human human tissue molecular pathology molecular weight nucleotide sequence protein domain protein expression protein function protein processing protein protein interaction regulator gene RWD containing SUMO enhancer gene signal transduction structure activity relation structure analysis amino acid sequence animal biology cell line chemical structure chemistry gene expression regulation genetics metabolism molecular genetics protein secondary structure Amino Acid Sequence Animals Cell Line Computational Biology Gene Expression Regulation Humans Hypoxia-Inducible Factor 1 Models, Molecular Molecular Sequence Data NF-kappa B Protein Isoforms Protein Structure, Secondary Signal Transduction SUMO-1 Protein Transcription Factors
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_19326203_v8_n2_p_Gerez
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paperaa:paper_19326203_v8_n2_p_Gerez
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spelling	paperaa:paper_19326203_v8_n2_p_Gerez2023-06-12T16:51:45Z In Silico Structural and Functional Characterization of the RSUME Splice Variants PLoS ONE 2013;8(2) Gerez, J. Fuertes, M. Tedesco, L. Silberstein, S. Sevlever, G. Paez-Pereda, M. Holsboer, F. Turjanski, A.G. Arzt, E. hypoxia inducible factor 1 immunoglobulin enhancer binding protein messenger RNA protein variant regulator protein RWD containing SUMO enhancer protein SUMO protein unclassified drug hypoxia inducible factor 1 immunoglobulin enhancer binding protein isoprotein RSUME protein, human SUMO 1 protein transcription factor article brain cancer carboxy terminal sequence computer model controlled study gene expression human human tissue molecular pathology molecular weight nucleotide sequence protein domain protein expression protein function protein processing protein protein interaction regulator gene RWD containing SUMO enhancer gene signal transduction structure activity relation structure analysis amino acid sequence animal biology cell line chemical structure chemistry gene expression regulation genetics metabolism molecular genetics protein secondary structure Amino Acid Sequence Animals Cell Line Computational Biology Gene Expression Regulation Humans Hypoxia-Inducible Factor 1 Models, Molecular Molecular Sequence Data NF-kappa B Protein Isoforms Protein Structure, Secondary Signal Transduction SUMO-1 Protein Transcription Factors 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-κB signaling pathway is inhibited and the HIF-1 pathway is increased more efficiently by the longest RSUME, by means of a greater physical interaction of RSUME267 with the target proteins. In addition, the mRNA and protein 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-κB 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. © 2013 Gerez et al. Fil:Gerez, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Silberstein, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Paez-Pereda, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Turjanski, A.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19326203_v8_n2_p_Gerez
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	hypoxia inducible factor 1 immunoglobulin enhancer binding protein messenger RNA protein variant regulator protein RWD containing SUMO enhancer protein SUMO protein unclassified drug hypoxia inducible factor 1 immunoglobulin enhancer binding protein isoprotein RSUME protein, human SUMO 1 protein transcription factor article brain cancer carboxy terminal sequence computer model controlled study gene expression human human tissue molecular pathology molecular weight nucleotide sequence protein domain protein expression protein function protein processing protein protein interaction regulator gene RWD containing SUMO enhancer gene signal transduction structure activity relation structure analysis amino acid sequence animal biology cell line chemical structure chemistry gene expression regulation genetics metabolism molecular genetics protein secondary structure Amino Acid Sequence Animals Cell Line Computational Biology Gene Expression Regulation Humans Hypoxia-Inducible Factor 1 Models, Molecular Molecular Sequence Data NF-kappa B Protein Isoforms Protein Structure, Secondary Signal Transduction SUMO-1 Protein Transcription Factors
spellingShingle	hypoxia inducible factor 1 immunoglobulin enhancer binding protein messenger RNA protein variant regulator protein RWD containing SUMO enhancer protein SUMO protein unclassified drug hypoxia inducible factor 1 immunoglobulin enhancer binding protein isoprotein RSUME protein, human SUMO 1 protein transcription factor article brain cancer carboxy terminal sequence computer model controlled study gene expression human human tissue molecular pathology molecular weight nucleotide sequence protein domain protein expression protein function protein processing protein protein interaction regulator gene RWD containing SUMO enhancer gene signal transduction structure activity relation structure analysis amino acid sequence animal biology cell line chemical structure chemistry gene expression regulation genetics metabolism molecular genetics protein secondary structure Amino Acid Sequence Animals Cell Line Computational Biology Gene Expression Regulation Humans Hypoxia-Inducible Factor 1 Models, Molecular Molecular Sequence Data NF-kappa B Protein Isoforms Protein Structure, Secondary Signal Transduction SUMO-1 Protein Transcription Factors Gerez, J. Fuertes, M. Tedesco, L. Silberstein, S. Sevlever, G. Paez-Pereda, M. Holsboer, F. Turjanski, A.G. Arzt, E. In Silico Structural and Functional Characterization of the RSUME Splice Variants
topic_facet	hypoxia inducible factor 1 immunoglobulin enhancer binding protein messenger RNA protein variant regulator protein RWD containing SUMO enhancer protein SUMO protein unclassified drug hypoxia inducible factor 1 immunoglobulin enhancer binding protein isoprotein RSUME protein, human SUMO 1 protein transcription factor article brain cancer carboxy terminal sequence computer model controlled study gene expression human human tissue molecular pathology molecular weight nucleotide sequence protein domain protein expression protein function protein processing protein protein interaction regulator gene RWD containing SUMO enhancer gene signal transduction structure activity relation structure analysis amino acid sequence animal biology cell line chemical structure chemistry gene expression regulation genetics metabolism molecular genetics protein secondary structure Amino Acid Sequence Animals Cell Line Computational Biology Gene Expression Regulation Humans Hypoxia-Inducible Factor 1 Models, Molecular Molecular Sequence Data NF-kappa B Protein Isoforms Protein Structure, Secondary Signal Transduction SUMO-1 Protein Transcription Factors
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-κB signaling pathway is inhibited and the HIF-1 pathway is increased more efficiently by the longest RSUME, by means of a greater physical interaction of RSUME267 with the target proteins. In addition, the mRNA and protein 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-κB 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. © 2013 Gerez et al.
format	Artículo Artículo publishedVersion
author	Gerez, J. Fuertes, M. Tedesco, L. Silberstein, S. Sevlever, G. Paez-Pereda, M. Holsboer, F. Turjanski, A.G. Arzt, E.
author_facet	Gerez, J. Fuertes, M. Tedesco, L. Silberstein, S. Sevlever, G. Paez-Pereda, M. Holsboer, F. Turjanski, A.G. Arzt, E.
author_sort	Gerez, J.
title	In Silico Structural and Functional Characterization of the RSUME Splice Variants
title_short	In Silico Structural and Functional Characterization of the RSUME Splice Variants
title_full	In Silico Structural and Functional Characterization of the RSUME Splice Variants
title_fullStr	In Silico Structural and Functional Characterization of the RSUME Splice Variants
title_full_unstemmed	In Silico Structural and Functional Characterization of the RSUME Splice Variants
title_sort	in silico structural and functional characterization of the rsume splice variants
publishDate	2013
url	http://hdl.handle.net/20.500.12110/paper_19326203_v8_n2_p_Gerez
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In Silico Structural and Functional Characterization of the RSUME Splice Variants

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