XPA deficiency affects the ubiquitin-proteasome system function
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/jspui/handle/123456789/29716 |
Resumo: | Xeroderma pigmentosum complementation group A (XPA), is defective in xeroderma pigmentosum patients, causing pre-disposition to skin cancer and neurological abnormalities, which is not well understood. Here, we analyzed the XPA-deficient cells transcriptional profile under oxidative stress. The imbalance in of ubiquitin-proteasome system (UPS) gene expression was observed in XPA-deficient cells and the involvement of nuclear factor erythroid 2-related factor-2 (NFE2L2) was indicated. Co-immunoprecipitation assays showed the interaction between XPA, apurinic-apyrimidinic endonuclease 1 (APE1) and NFE2L2 proteins. Decreased NFE2L2 protein expression and proteasome activity was also observed in XPA-deficient cells. The data suggest the involvement of the growth arrest and DNA-damage-inducible beta (GADD45β) in NFE2L2 functions. Similar results were obtained in xpa-1 (RNAi) Caenorhabditis elegans suggesting the conservation of XPA and NFE2L2 interactions. In conclusion, stress response activation occurs in XPA-deficient cells under oxidative stress; however, these cells fail to activate the UPS cytoprotective response, which may contribute to XPA patient’s phenotypes. |
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Leal, Angélica Maria de SousaMedeiros, Lázaro Batista de AzevedoMuñoz-Cadavid, Cesar OrlandoOliveira, Riva de PaulaTimóteo, Ana Rafaela de SouzaOliveira, Ana Helena Sales deFaustino, André Luis FonsecaSilva, Vandeclécio Lira daSouza, Sandro José deLajus, Tirzah Braz PettaCampos, Julliane Tamara Araújo de MeloAgnez-Lima, Lucymara Fassarella2020-07-23T17:36:23Z2020-07-23T17:36:23Z2020-07LEAL, Angélica Maria de Sousa; MEDEIROS, Lázaro Batista de Azevedo; MUÑOZ-CADAVID, Cesar Orlando; OLIVEIRA, Riva de Paula; TIMÓTEO, Ana Rafaela de Souza; OLIVEIRA, Ana Helena Sales de; FAUSTINO, André Luis Fonseca; SILVA, Vandeclécio Lira da; SOUZA, Sandro José de; LAJUS, Tirzah Braz Petta. XPA deficiency affects the ubiquitin-proteasome system function. Dna Repair, [S.L.], v. 94, p. 102937, out. 2020. http://dx.doi.org/10.1016/j.dnarep.2020.102937. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S1568786420301865?via%3Dihub. Acesso em: 23 jul. 2020.https://repositorio.ufrn.br/jspui/handle/123456789/2971610.1016/j.dnarep.2020.102937ElsevierAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessXeroderma pigmentosumOxidative stressXeroderma Pigmentosum Group A ProteinApurinic-apyrimidinic endonuclease 1 (APE1)NF-E2-Related Factor 2Transcriptional regulationProteolysisProteostasisProteasomeXPA deficiency affects the ubiquitin-proteasome system functioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleXeroderma pigmentosum complementation group A (XPA), is defective in xeroderma pigmentosum patients, causing pre-disposition to skin cancer and neurological abnormalities, which is not well understood. Here, we analyzed the XPA-deficient cells transcriptional profile under oxidative stress. The imbalance in of ubiquitin-proteasome system (UPS) gene expression was observed in XPA-deficient cells and the involvement of nuclear factor erythroid 2-related factor-2 (NFE2L2) was indicated. Co-immunoprecipitation assays showed the interaction between XPA, apurinic-apyrimidinic endonuclease 1 (APE1) and NFE2L2 proteins. Decreased NFE2L2 protein expression and proteasome activity was also observed in XPA-deficient cells. The data suggest the involvement of the growth arrest and DNA-damage-inducible beta (GADD45β) in NFE2L2 functions. Similar results were obtained in xpa-1 (RNAi) Caenorhabditis elegans suggesting the conservation of XPA and NFE2L2 interactions. In conclusion, stress response activation occurs in XPA-deficient cells under oxidative stress; however, these cells fail to activate the UPS cytoprotective response, which may contribute to XPA patient’s phenotypes.engreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufrn.br/bitstream/123456789/29716/2/license_rdfe39d27027a6cc9cb039ad269a5db8e34MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81484https://repositorio.ufrn.br/bitstream/123456789/29716/3/license.txte9597aa2854d128fd968be5edc8a28d9MD53TEXTXPADeficiencyAffects_Souza_2020.pdf.txtXPADeficiencyAffects_Souza_2020.pdf.txtExtracted texttext/plain75099https://repositorio.ufrn.br/bitstream/123456789/29716/4/XPADeficiencyAffects_Souza_2020.pdf.txt68422e5fa04ab4f6c3caf3f3e02e6185MD54THUMBNAILXPADeficiencyAffects_Souza_2020.pdf.jpgXPADeficiencyAffects_Souza_2020.pdf.jpgGenerated Thumbnailimage/jpeg1516https://repositorio.ufrn.br/bitstream/123456789/29716/5/XPADeficiencyAffects_Souza_2020.pdf.jpg363b644c87e467b9f3e6310286afcc99MD55123456789/297162023-02-02 18:10:18.156oai:https://repositorio.ufrn.br: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Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2023-02-02T21:10:18Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pt_BR.fl_str_mv |
XPA deficiency affects the ubiquitin-proteasome system function |
title |
XPA deficiency affects the ubiquitin-proteasome system function |
spellingShingle |
XPA deficiency affects the ubiquitin-proteasome system function Leal, Angélica Maria de Sousa Xeroderma pigmentosum Oxidative stress Xeroderma Pigmentosum Group A Protein Apurinic-apyrimidinic endonuclease 1 (APE1) NF-E2-Related Factor 2 Transcriptional regulation Proteolysis Proteostasis Proteasome |
title_short |
XPA deficiency affects the ubiquitin-proteasome system function |
title_full |
XPA deficiency affects the ubiquitin-proteasome system function |
title_fullStr |
XPA deficiency affects the ubiquitin-proteasome system function |
title_full_unstemmed |
XPA deficiency affects the ubiquitin-proteasome system function |
title_sort |
XPA deficiency affects the ubiquitin-proteasome system function |
author |
Leal, Angélica Maria de Sousa |
author_facet |
Leal, Angélica Maria de Sousa Medeiros, Lázaro Batista de Azevedo Muñoz-Cadavid, Cesar Orlando Oliveira, Riva de Paula Timóteo, Ana Rafaela de Souza Oliveira, Ana Helena Sales de Faustino, André Luis Fonseca Silva, Vandeclécio Lira da Souza, Sandro José de Lajus, Tirzah Braz Petta Campos, Julliane Tamara Araújo de Melo Agnez-Lima, Lucymara Fassarella |
author_role |
author |
author2 |
Medeiros, Lázaro Batista de Azevedo Muñoz-Cadavid, Cesar Orlando Oliveira, Riva de Paula Timóteo, Ana Rafaela de Souza Oliveira, Ana Helena Sales de Faustino, André Luis Fonseca Silva, Vandeclécio Lira da Souza, Sandro José de Lajus, Tirzah Braz Petta Campos, Julliane Tamara Araújo de Melo Agnez-Lima, Lucymara Fassarella |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Leal, Angélica Maria de Sousa Medeiros, Lázaro Batista de Azevedo Muñoz-Cadavid, Cesar Orlando Oliveira, Riva de Paula Timóteo, Ana Rafaela de Souza Oliveira, Ana Helena Sales de Faustino, André Luis Fonseca Silva, Vandeclécio Lira da Souza, Sandro José de Lajus, Tirzah Braz Petta Campos, Julliane Tamara Araújo de Melo Agnez-Lima, Lucymara Fassarella |
dc.subject.por.fl_str_mv |
Xeroderma pigmentosum Oxidative stress Xeroderma Pigmentosum Group A Protein Apurinic-apyrimidinic endonuclease 1 (APE1) NF-E2-Related Factor 2 Transcriptional regulation Proteolysis Proteostasis Proteasome |
topic |
Xeroderma pigmentosum Oxidative stress Xeroderma Pigmentosum Group A Protein Apurinic-apyrimidinic endonuclease 1 (APE1) NF-E2-Related Factor 2 Transcriptional regulation Proteolysis Proteostasis Proteasome |
description |
Xeroderma pigmentosum complementation group A (XPA), is defective in xeroderma pigmentosum patients, causing pre-disposition to skin cancer and neurological abnormalities, which is not well understood. Here, we analyzed the XPA-deficient cells transcriptional profile under oxidative stress. The imbalance in of ubiquitin-proteasome system (UPS) gene expression was observed in XPA-deficient cells and the involvement of nuclear factor erythroid 2-related factor-2 (NFE2L2) was indicated. Co-immunoprecipitation assays showed the interaction between XPA, apurinic-apyrimidinic endonuclease 1 (APE1) and NFE2L2 proteins. Decreased NFE2L2 protein expression and proteasome activity was also observed in XPA-deficient cells. The data suggest the involvement of the growth arrest and DNA-damage-inducible beta (GADD45β) in NFE2L2 functions. Similar results were obtained in xpa-1 (RNAi) Caenorhabditis elegans suggesting the conservation of XPA and NFE2L2 interactions. In conclusion, stress response activation occurs in XPA-deficient cells under oxidative stress; however, these cells fail to activate the UPS cytoprotective response, which may contribute to XPA patient’s phenotypes. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-07-23T17:36:23Z |
dc.date.available.fl_str_mv |
2020-07-23T17:36:23Z |
dc.date.issued.fl_str_mv |
2020-07 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
LEAL, Angélica Maria de Sousa; MEDEIROS, Lázaro Batista de Azevedo; MUÑOZ-CADAVID, Cesar Orlando; OLIVEIRA, Riva de Paula; TIMÓTEO, Ana Rafaela de Souza; OLIVEIRA, Ana Helena Sales de; FAUSTINO, André Luis Fonseca; SILVA, Vandeclécio Lira da; SOUZA, Sandro José de; LAJUS, Tirzah Braz Petta. XPA deficiency affects the ubiquitin-proteasome system function. Dna Repair, [S.L.], v. 94, p. 102937, out. 2020. http://dx.doi.org/10.1016/j.dnarep.2020.102937. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S1568786420301865?via%3Dihub. Acesso em: 23 jul. 2020. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/jspui/handle/123456789/29716 |
dc.identifier.doi.none.fl_str_mv |
10.1016/j.dnarep.2020.102937 |
identifier_str_mv |
LEAL, Angélica Maria de Sousa; MEDEIROS, Lázaro Batista de Azevedo; MUÑOZ-CADAVID, Cesar Orlando; OLIVEIRA, Riva de Paula; TIMÓTEO, Ana Rafaela de Souza; OLIVEIRA, Ana Helena Sales de; FAUSTINO, André Luis Fonseca; SILVA, Vandeclécio Lira da; SOUZA, Sandro José de; LAJUS, Tirzah Braz Petta. XPA deficiency affects the ubiquitin-proteasome system function. Dna Repair, [S.L.], v. 94, p. 102937, out. 2020. http://dx.doi.org/10.1016/j.dnarep.2020.102937. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S1568786420301865?via%3Dihub. Acesso em: 23 jul. 2020. 10.1016/j.dnarep.2020.102937 |
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eng |
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Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ |
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Elsevier |
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