Cryptococcus neoformans Prp8 Intein: An In Vivo Target-Based Drug Screening System in Saccharomyces cerevisiae to Identify Protein Splicing Inhibitors and Explore Its Dynamics

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Autor(es): dc.contributorFederal University of Rio Grande do Norte (UFRN)-
Autor(es): dc.contributorThe University of Ottawa-
Autor(es): dc.contributorUniversidade Federal de Goiás (UFG)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorSão Paulo-
Autor(es): dc.contributorDalhousie University-
Autor(es): dc.creatorFernandes, José Alex Lourenço-
Autor(es): dc.creatorZatti, Matheus da Silva-
Autor(es): dc.creatorArantes, Thales Domingos-
Autor(es): dc.creatorSouza, Maria Fernanda Bezerra de-
Autor(es): dc.creatorSantoni, Mariana Marchi-
Autor(es): dc.creatorRossi, Danuza-
Autor(es): dc.creatorZanelli, Cleslei Fernando-
Autor(es): dc.creatorLiu, Xiang-Qin-
Autor(es): dc.creatorBagagli, Eduardo-
Autor(es): dc.creatorTheodoro, Raquel Cordeiro-
Data de aceite: dc.date.accessioned2025-08-21T22:42:42Z-
Data de disponibilização: dc.date.available2025-08-21T22:42:42Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-08-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/jof8080846-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/241608-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/241608-
Descrição: dc.descriptionInteins are genetic mobile elements that are inserted within protein-coding genes, which are usually housekeeping genes. They are transcribed and translated along with the host gene, then catalyze their own splicing out of the host protein, which assumes its functional conformation thereafter. As Prp8 inteins are found in several important fungal pathogens and are absent in mammals, they are considered potential therapeutic targets since inhibiting their splicing would selectively block the maturation of fungal proteins. We developed a target-based drug screening system to evaluate the splicing of Prp8 intein from the yeast pathogen Cryptococcus neoformans (CnePrp8i) using Saccharomyces cerevisiae Ura3 as a non-native host protein. In our heterologous system, intein splicing preserved the full functionality of Ura3. To validate the system for drug screening, we examined cisplatin, which has been described as an intein splicing inhibitor. By using our system, new potential protein splicing inhibitors may be identified and used, in the future, as a new class of drugs for mycosis treatment. Our system also greatly facilitates the visualization of CnePrp8i splicing dynamics in vivo.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionInstitute of Tropical Medicine Federal University of Rio Grande do Norte (UFRN), Rio Grande do Norte-
Descrição: dc.descriptionDepartment of Biochemistry Biosciences Center Federal University of Rio Grande do Norte (UFRN), Rio Grande do Norte-
Descrição: dc.descriptionOttawa Hospital Research Institute (OHRI) The University of Ottawa-
Descrição: dc.descriptionDepartment of Biosciences and Technology Institute of Tropical Pathology and Public Health Federal University of Goiás, Goiânia-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences São Paulo State University (UNESP), São Paulo-
Descrição: dc.descriptionPensabio São Paulo-
Descrição: dc.descriptionDepartment of Biochemistry and Molecular Biology Dalhousie University-
Descrição: dc.descriptionMicrobiology and Immunology Department Biosciences Institute of Botucatu São Paulo State University (UNESP), São Paulo-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences São Paulo State University (UNESP), São Paulo-
Descrição: dc.descriptionMicrobiology and Immunology Department Biosciences Institute of Botucatu São Paulo State University (UNESP), São Paulo-
Descrição: dc.descriptionCNPq: 475525/2013-2-
Idioma: dc.languageen-
Relação: dc.relationJournal of Fungi-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectcisplatin-
Palavras-chave: dc.subjectCnePrp8i-
Palavras-chave: dc.subjectinhibitor screening-
Palavras-chave: dc.subjectintein-
Palavras-chave: dc.subjectnovel drug target-
Palavras-chave: dc.subjectprotein splicing-
Palavras-chave: dc.subjectPrp8-
Palavras-chave: dc.subjectUra3-
Título: dc.titleCryptococcus neoformans Prp8 Intein: An In Vivo Target-Based Drug Screening System in Saccharomyces cerevisiae to Identify Protein Splicing Inhibitors and Explore Its Dynamics-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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