XPA deficiency affects the ubiquitin-proteasome system function

Detalhes bibliográficos
Autor(a) principal: Leal, Angélica Maria de Sousa
Data de Publicação: 2020
Outros Autores: 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
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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spelling 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:123456789/29716Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKCkJ5IHNpZ25pbmcgYW5kIGRlbGl2ZXJpbmcgdGhpcyBsaWNlbnNlLCBNci4gKGF1dGhvciBvciBjb3B5cmlnaHQgaG9sZGVyKToKCgphKSBHcmFudHMgdGhlIFVuaXZlcnNpZGFkZSBGZWRlcmFsIFJpbyBHcmFuZGUgZG8gTm9ydGUgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgb2YKcmVwcm9kdWNlLCBjb252ZXJ0IChhcyBkZWZpbmVkIGJlbG93KSwgY29tbXVuaWNhdGUgYW5kIC8gb3IKZGlzdHJpYnV0ZSB0aGUgZGVsaXZlcmVkIGRvY3VtZW50IChpbmNsdWRpbmcgYWJzdHJhY3QgLyBhYnN0cmFjdCkgaW4KZGlnaXRhbCBvciBwcmludGVkIGZvcm1hdCBhbmQgaW4gYW55IG1lZGl1bS4KCmIpIERlY2xhcmVzIHRoYXQgdGhlIGRvY3VtZW50IHN1Ym1pdHRlZCBpcyBpdHMgb3JpZ2luYWwgd29yaywgYW5kIHRoYXQKeW91IGhhdmUgdGhlIHJpZ2h0IHRvIGdyYW50IHRoZSByaWdodHMgY29udGFpbmVkIGluIHRoaXMgbGljZW5zZS4gRGVjbGFyZXMKdGhhdCB0aGUgZGVsaXZlcnkgb2YgdGhlIGRvY3VtZW50IGRvZXMgbm90IGluZnJpbmdlLCBhcyBmYXIgYXMgaXQgaXMKdGhlIHJpZ2h0cyBvZiBhbnkgb3RoZXIgcGVyc29uIG9yIGVudGl0eS4KCmMpIElmIHRoZSBkb2N1bWVudCBkZWxpdmVyZWQgY29udGFpbnMgbWF0ZXJpYWwgd2hpY2ggZG9lcyBub3QKcmlnaHRzLCBkZWNsYXJlcyB0aGF0IGl0IGhhcyBvYnRhaW5lZCBhdXRob3JpemF0aW9uIGZyb20gdGhlIGhvbGRlciBvZiB0aGUKY29weXJpZ2h0IHRvIGdyYW50IHRoZSBVbml2ZXJzaWRhZGUgRmVkZXJhbCBkbyBSaW8gR3JhbmRlIGRvIE5vcnRlIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdCB0aGlzIG1hdGVyaWFsIHdob3NlIHJpZ2h0cyBhcmUgb2YKdGhpcmQgcGFydGllcyBpcyBjbGVhcmx5IGlkZW50aWZpZWQgYW5kIHJlY29nbml6ZWQgaW4gdGhlIHRleHQgb3IKY29udGVudCBvZiB0aGUgZG9jdW1lbnQgZGVsaXZlcmVkLgoKSWYgdGhlIGRvY3VtZW50IHN1Ym1pdHRlZCBpcyBiYXNlZCBvbiBmdW5kZWQgb3Igc3VwcG9ydGVkIHdvcmsKYnkgYW5vdGhlciBpbnN0aXR1dGlvbiBvdGhlciB0aGFuIHRoZSBVbml2ZXJzaWRhZGUgRmVkZXJhbCBkbyBSaW8gR3JhbmRlIGRvIE5vcnRlLCBkZWNsYXJlcyB0aGF0IGl0IGhhcyBmdWxmaWxsZWQgYW55IG9ibGlnYXRpb25zIHJlcXVpcmVkIGJ5IHRoZSByZXNwZWN0aXZlIGFncmVlbWVudCBvciBhZ3JlZW1lbnQuCgpUaGUgVW5pdmVyc2lkYWRlIEZlZGVyYWwgZG8gUmlvIEdyYW5kZSBkbyBOb3J0ZSB3aWxsIGNsZWFybHkgaWRlbnRpZnkgaXRzIG5hbWUgKHMpIGFzIHRoZSBhdXRob3IgKHMpIG9yIGhvbGRlciAocykgb2YgdGhlIGRvY3VtZW50J3MgcmlnaHRzCmRlbGl2ZXJlZCwgYW5kIHdpbGwgbm90IG1ha2UgYW55IGNoYW5nZXMsIG90aGVyIHRoYW4gdGhvc2UgcGVybWl0dGVkIGJ5CnRoaXMgbGljZW5zZQo=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
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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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