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DEGRON PATHWAYS AND LEISHMANIASIS: DEBATING POTENTIAL ROLES OF LEISHMANIA SPP. PROTEASES ACTIVITY ON GUIDING HOSTS IMMUNE RESPONSE AND THEIR RELEVANCE TO THE DEVELOPMENT OF VACCINES
Degron
Proteases de cisteína
Proteases de serina
Resposta imune
Citocinas
Fatores de transcrição
Degron
Cysteine proteases
Serine proteases
Immune response
Cytokines
Transcription factors
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de janeiro, RJ, Brasil.
Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Niterói, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Universidade Iguaçu. Nova Iguaçu, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de janeiro, RJ, Brasil.
Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Niterói, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Universidade Iguaçu. Nova Iguaçu, RJ, Brasil.
Abstract
Degrons are short peptide sequences that signalize target sites for protein degradation by proteases. Herein, we bring forth the discussion on degrons present in proteins related to the immune system of Mus musculus that are potential targets for cysteine and serine proteases of Leishmania spp. and their possible roles on host immune regulation by parasites. The Merops database was used to identify protease substrates and proteases sequence motifs, while MAST/MEME Suite was applied to find degron motifs in murine cytokines (IFN-y, IL-4, IL-5, IL-13, IL-17) and transcription factors (NF-kappaB, STAT-1, AP-1, CREB, and BACH2). STRING tool was used to construct an interaction network for the immune factors and SWISS-MODEL server to generate three-dimensional models of proteins. In silico assays confirm the occurrence of degrons in the selected immune response factors. Further analyses were conducted only in those with resolved three-dimensional structures. The predicted interaction network of degron-containing M. musculus proteins shows the possibility that the specific activity of parasite proteases could interfere with the trend of Th1/Th2 immune responses. Data suggest that degrons may play a role in the immune responses in leishmaniases as targets for parasite proteases activity, directing the degradation of specific immune-related factors.
Keywords in Portuguese
Leishmania sppDegron
Proteases de cisteína
Proteases de serina
Resposta imune
Citocinas
Fatores de transcrição
Keywords
Leishmania sppDegron
Cysteine proteases
Serine proteases
Immune response
Cytokines
Transcription factors
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