Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunit
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/28810 |
Resumo: | Centro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brasil. / Universidade Estadual de Campinas. Instituto de Biologia. Campinas, SP, Brasil. |
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Migueleti, Deivid L. S.Smetana, Juliana H. C.Nunes, Hugo F.Kobarg, JörgZanchin, Nilson Ivo Tonin2018-09-14T19:47:44Z2018-09-14T19:47:44Z2012MIGUELETI, Deivid L. S. et al. Identification and Characterization of an Alternatively Spliced Isoform of the Human Protein Phosphatase 2Aα Catalytic Subunit. Journal of Biological Chemistry, v. 287, n.7, p. 4853 -4862, 2012.0021-9258https://www.arca.fiocruz.br/handle/icict/2881010.1074/jbc.M111.2833411083-351XporAmerican Society for Biochemistry and Molecular BiologyPP2AProtein Tyrosine PhosphatasesRNA IsoformsHoloenzymesRNAProteínas Tirosina FosfatasasIsoformas de ARNARNProteínas Tirosina FosfatasesIsoformas de RNAHoloenzimasRNA MensageiroIdentification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunitinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCentro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brasil. / Universidade Estadual de Campinas. Instituto de Biologia. Campinas, SP, Brasil.Centro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brasil.Universidade Estadual de Campinas. Centro de Biologia Molecular e Engenharia Genética, Campinas, SP, Brasil.Centro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brasil. / Universidade Estadual de Campinas. Instituto de Biologia. Campinas, SP, Brasil.Universidade Estadual de Campinas. Centro de Biologia Molecular e Engenharia Genética, Campinas, SP, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.PP2A is the main serine/threonine-specific phosphatase in animal cells. The active phosphatase has been described as a holoenzyme consisting of a catalytic, a scaffolding, and a variable regulatory subunit, all encoded by multiple genes, allowing for the assembly of more than 70 different holoenzymes. The catalytic subunit can also interact with α4, TIPRL (TIP41, TOR signaling pathway regulator-like), the methyl-transferase LCMT-1, and the methyl-esterase PME-1. Here, we report that the gene encoding the catalytic subunit PP2Acα can generate two mRNA types, the standard mRNA and a shorter isoform, lacking exon 5, which we termed PP2Acα2. Higher levels of the PP2Acα2 mRNA, equivalent to the level of the longer PP2Acα mRNA, were detected in peripheral blood mononuclear cells that were left to rest for 24 h. After this time, the peripheral blood mononuclear cells are still viable and the PP2Acα2 mRNA decreases soon after they are transferred to culture medium, showing that generation of the shorter isoform depends on the incubation conditions. FLAG-tagged PP2Acα2 expressed in HEK293 is catalytically inactive. It displays a specific interaction profile with enhanced binding to the α4 regulatory subunit, but no binding to the scaffolding subunit and PME-1. Consistently, α4 out-competes PME-1 and LCMT-1 for binding to both PP2Acα isoforms in pulldown assays. Together with molecular modeling studies, this suggests that all three regulators share a common binding surface on the catalytic subunit. Our findings add important new insights into the complex mechanisms of PP2A regulation.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83084https://www.arca.fiocruz.br/bitstream/icict/28810/1/license.txt783568c2893d2e25a99990b126be1772MD51ORIGINALJournalBiolChemistryzb4853.pdfJournalBiolChemistryzb4853.pdfapplication/pdf1990964https://www.arca.fiocruz.br/bitstream/icict/28810/2/JournalBiolChemistryzb4853.pdfbb68ee6b122af42a80fca5054d5c4a3dMD52TEXTJournalBiolChemistryzb4853.pdf.txtJournalBiolChemistryzb4853.pdf.txtExtracted texttext/plain50944https://www.arca.fiocruz.br/bitstream/icict/28810/3/JournalBiolChemistryzb4853.pdf.txt3b480c704446492dbe71882f4e528434MD53icict/288102018-09-19 16:10:58.085oai:www.arca.fiocruz.br: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ório 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dc.title.pt_BR.fl_str_mv |
Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunit |
title |
Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunit |
spellingShingle |
Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunit Migueleti, Deivid L. S. PP2A Protein Tyrosine Phosphatases RNA Isoforms Holoenzymes RNA Proteínas Tirosina Fosfatasas Isoformas de ARN ARN Proteínas Tirosina Fosfatases Isoformas de RNA Holoenzimas RNA Mensageiro |
title_short |
Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunit |
title_full |
Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunit |
title_fullStr |
Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunit |
title_full_unstemmed |
Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunit |
title_sort |
Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunit |
author |
Migueleti, Deivid L. S. |
author_facet |
Migueleti, Deivid L. S. Smetana, Juliana H. C. Nunes, Hugo F. Kobarg, Jörg Zanchin, Nilson Ivo Tonin |
author_role |
author |
author2 |
Smetana, Juliana H. C. Nunes, Hugo F. Kobarg, Jörg Zanchin, Nilson Ivo Tonin |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Migueleti, Deivid L. S. Smetana, Juliana H. C. Nunes, Hugo F. Kobarg, Jörg Zanchin, Nilson Ivo Tonin |
dc.subject.other.pt_BR.fl_str_mv |
PP2A |
topic |
PP2A Protein Tyrosine Phosphatases RNA Isoforms Holoenzymes RNA Proteínas Tirosina Fosfatasas Isoformas de ARN ARN Proteínas Tirosina Fosfatases Isoformas de RNA Holoenzimas RNA Mensageiro |
dc.subject.en.pt_BR.fl_str_mv |
Protein Tyrosine Phosphatases RNA Isoforms Holoenzymes RNA |
dc.subject.es.pt_BR.fl_str_mv |
Proteínas Tirosina Fosfatasas Isoformas de ARN ARN |
dc.subject.decs.pt_BR.fl_str_mv |
Proteínas Tirosina Fosfatases Isoformas de RNA Holoenzimas RNA Mensageiro |
description |
Centro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brasil. / Universidade Estadual de Campinas. Instituto de Biologia. Campinas, SP, Brasil. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012 |
dc.date.accessioned.fl_str_mv |
2018-09-14T19:47:44Z |
dc.date.available.fl_str_mv |
2018-09-14T19:47:44Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
MIGUELETI, Deivid L. S. et al. Identification and Characterization of an Alternatively Spliced Isoform of the Human Protein Phosphatase 2Aα Catalytic Subunit. Journal of Biological Chemistry, v. 287, n.7, p. 4853 -4862, 2012. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/28810 |
dc.identifier.issn.pt_BR.fl_str_mv |
0021-9258 |
dc.identifier.doi.none.fl_str_mv |
10.1074/jbc.M111.283341 |
dc.identifier.eissn.none.fl_str_mv |
1083-351X |
identifier_str_mv |
MIGUELETI, Deivid L. S. et al. Identification and Characterization of an Alternatively Spliced Isoform of the Human Protein Phosphatase 2Aα Catalytic Subunit. Journal of Biological Chemistry, v. 287, n.7, p. 4853 -4862, 2012. 0021-9258 10.1074/jbc.M111.283341 1083-351X |
url |
https://www.arca.fiocruz.br/handle/icict/28810 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
American Society for Biochemistry and Molecular Biology |
publisher.none.fl_str_mv |
American Society for Biochemistry and Molecular Biology |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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Fundação Oswaldo Cruz (FIOCRUZ) |
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FIOCRUZ |
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FIOCRUZ |
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Repositório Institucional da FIOCRUZ (ARCA) |
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Repositório Institucional da FIOCRUZ (ARCA) |
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