Proteomic and interactome approaches reveal PAK4, PHB-2, and 14-3-3n as targets of overactivated Cdc42 in cellular responses to genomic instability
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor | Laboratório Especial de Toxinologia Aplicada (LETA) | pt_BR |
dc.contributor.author | Silva, Luiz E. | pt_BR |
dc.contributor.author | Souza, Renan C. | pt_BR |
dc.contributor.author | Kitano, Eduardo Shigueo | pt_BR |
dc.contributor.author | Monteiro, Lucas F. | pt_BR |
dc.contributor.author | Iwai, Leo Kei | pt_BR |
dc.contributor.author | Forti, Fabio L. | pt_BR |
dc.date.accessioned | 2020-07-09T21:25:31Z | - |
dc.date.available | 2020-07-09T21:25:31Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Silva LE., Souza RC., Kitano ES, Monteiro LF., Iwai LK, Forti FL.. Proteomic and interactome approaches reveal PAK4, PHB-2, and 14-3-3n as targets of overactivated Cdc42 in cellular responses to genomic instability. J. proteome res.. 2019 Sep;18(10):3597-3614. doi:10.1021/acs.jproteome.9b00260. | pt_BR |
dc.identifier.issn | 1535-3893 | - |
dc.identifier.issn | 1535-3907 | - |
dc.identifier.uri | https://repositorio.butantan.gov.br/handle/butantan/2864 | - |
dc.description.abstract | Cdc42, a member of the Rho GTPase family, is an intracellular signaling protein known for its roles in cytoskeleton rearrangements and, more recently, in apoptosis/senescence triggered by genotoxic stress. In some tumor cells, the overactivation of Cdc42 through the expression of constitutively active mutants (G12V or Q61L), GEF activation, or GAP downregulation functions as an antiproliferative or pro-aging mechanism. In this study, human cell lines with different P53 protein profiles were exposed to UV radiation, and the interactions between Cdc42 and proteins that are putatively involved in the DNA damage response and repair mechanisms were screened. The affinity-purified proteins obtained through pull-down experiments of the cell lysates using the recombinant protein baits GST, GST-Cdc42-WT, or GST-Cdc42-G12V were identified by mass spectrometry. The resulting data were filtered and used for the construction of protein–protein interaction networks. Among several promising proteins, three targets, namely, PAK4, PHB-2, and 14-3-3?, which are involved in the cell cycle, apoptosis, DNA repair, and chromatin remodeling processes, were identified. Biochemical validation experiments showed physical and proximal interactions between Cdc42 and the three targets in the cells, particularly after exposure to UV. The results suggest that the molecular mechanisms coordinated by overactivated Cdc42 (with the G12V mutation) to increase the cellular sensitivity to UV radiation and the susceptibility to cell death are collectively mediated by these three proteins. Therefore, the Cdc42 GTPase can potentially be considered another player involved in maintenance of the genomic stability of human cells during exposure to genotoxic stress. | pt_BR |
dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) | pt_BR |
dc.description.sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) | pt_BR |
dc.description.sponsorship | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) | pt_BR |
dc.format.extent | 3597-3614 | pt_BR |
dc.language | eng | pt_BR |
dc.publisher | American Chemical Society | pt_BR |
dc.relation.ispartof | Journal of Proteome Research | pt_BR |
dc.title | Proteomic and interactome approaches reveal PAK4, PHB-2, and 14-3-3n as targets of overactivated Cdc42 in cellular responses to genomic instability | pt_BR |
dc.type | Article | pt_BR |
dc.identifier.doi | 10.1021/acs.jproteome.9b00260 | pt_BR |
dc.identifier.url | https://doi.org/10.1021/acs.jproteome.9b00260 | pt_BR |
dc.contributor.external | Universidade de São Paulo (USP)¦¦Brasil | pt_BR |
dc.publisher.city | Washington | pt_BR |
dc.identifier.citationvolume | 18 | pt_BR |
dc.identifier.citationissue | 10 | pt_BR |
dc.subject.keyword | genomic instability | pt_BR |
dc.subject.keyword | Cdc42 | pt_BR |
dc.subject.keyword | ultraviolet radiation | pt_BR |
dc.subject.keyword | affinity purification | pt_BR |
dc.subject.keyword | mass spectrometry | pt_BR |
dc.subject.keyword | interactome | pt_BR |
dc.subject.keyword | protein-protein interaction | pt_BR |
dc.relation.ispartofabbreviated | J. proteome res. | pt_BR |
dc.identifier.citationabnt | v. 18, n. 10, p. 3597-3614, sep. 2019 | pt_BR |
dc.identifier.citationvancouver | 2019 Sep;18(10):3597-3614 | pt_BR |
dc.publisher.country | United States | pt_BR |
dc.contributor.butantan | Iwai, Leo Kei|:Pesquisador:Docente Colaborador PPGTOX|:Laboratório Especial de Toxinologia Aplicada (LETA)|: | pt_BR |
dc.contributor.butantan | Kitano, Eduardo Shigueo|:Aluno|:Laboratório Especial de Toxinologia Aplicada (LETA)|: | pt_BR |
dc.sponsorship.butantan | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦230420/2016/7 | pt_BR |
dc.sponsorship.butantan | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)¦¦88887.136364/2017-00 | pt_BR |
dc.sponsorship.butantan | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2008/58264-5 | pt_BR |
dc.sponsorship.butantan | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2015/03983-0 | pt_BR |
dc.sponsorship.butantan | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2018/01753-6 | pt_BR |
dc.sponsorship.butantan | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/07467-1 | pt_BR |
dc.identifier.bvscc | BR78.1 | pt_BR |
dc.identifier.bvsdb | IBProd | pt_BR |
item.openairetype | Article | - |
item.fulltext | Com Texto completo | - |
item.grantfulltext | embargo_29990101 | - |
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