Functional characterization of Cullin-1-RING ubiquitin ligase (CRL1) complex in Leishmania infantum

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Autor(es): dc.contributorUniversidade Federal de São Carlos (UFSCar)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversity of Glasgow-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade Estadual de Campinas (UNICAMP)-
Autor(es): dc.creatorde Correia, Camila Rolemberg Santana Travaglini Berti-
Autor(es): dc.creatorTorres, Caroline-
Autor(es): dc.creatorGomes, Ellen-
Autor(es): dc.creatorRodriguez, Giovana Maffei-
Autor(es): dc.creatorRegatieri, Wesley Klaysson Pereira-
Autor(es): dc.creatorTakamiya, Nayore Tamie-
Autor(es): dc.creatorRogerio, Luana Aparecida-
Autor(es): dc.creatorMalavazi, Iran-
Autor(es): dc.creatorGomes, Marcelo Damário-
Autor(es): dc.creatorDamasceno, Jeziel Dener-
Autor(es): dc.creatorda Silva, Vitor Luiz-
Autor(es): dc.creatorde Oliveira, Marcos Antonio Fernandes-
Autor(es): dc.creatorda Silva, Marcelo Santos-
Autor(es): dc.creatorNascimento, Alessandro Silva-
Autor(es): dc.creatorCoelho, Adriano Cappellazzo-
Autor(es): dc.creatorMaruyama, Sandra Regina-
Autor(es): dc.creatorTeixeira, Felipe Roberti-
Data de aceite: dc.date.accessioned2025-08-21T22:49:55Z-
Data de disponibilização: dc.date.available2025-08-21T22:49:55Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-07-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1371/journal.ppat.1012336-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/309417-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/309417-
Descrição: dc.descriptionCullin-1-RING ubiquitin ligases (CRL1) or SCF1 (SKP1-CUL1-RBX1) E3 ubiquitin ligases are the largest and most extensively investigated class of E3 ligases in mammals that regulate fundamental processes, such as the cell cycle and proliferation. These enzymes are multiprotein complexes comprising SKP1, CUL1, RBX1, and an F-box protein that acts as a specificity factor by interacting with SKP1 through its F-box domain and recruiting substrates via other domains. E3 ligases are important players in the ubiquitination process, recognizing and transferring ubiquitin to substrates destined for degradation by proteasomes or processing by deubiquitinating enzymes. The ubiquitin-proteasome system (UPS) is the main regulator of intracellular proteolysis in eukaryotes and is required for parasites to alternate hosts in their life cycles, resulting in successful parasitism. Leishmania UPS is poorly investigated, and CRL1 in L. infantum, the causative agent of visceral leishmaniasis in Latin America, is yet to be described. Here, we show that the L. infantum genes LINF_110018100 (SKP1-like protein), LINF_240029100 (cullin-like protein-like protein), and LINF_210005300 (ring-box protein 1 –putative) form a LinfCRL1 complex structurally similar to the H. sapiens CRL1. Mass spectrometry analysis of the LinfSkp1 and LinfCul1 interactomes revealed proteins involved in several intracellular processes, including six F-box proteins known as F-box-like proteins (Flp) (data are available via ProteomeXchange with identifier PXD051961). The interaction of LinfFlp 1–6 with LinfSkp1 was confirmed, and using in vitro ubiquitination assays, we demonstrated the function of the LinfCRL1(Flp1) complex to transfer ubiquitin. We also found that LinfSKP1 and LinfRBX1 knockouts resulted in nonviable L. infantum lineages, whereas LinfCUL1 was involved in parasite growth and rosette formation. Finally, our results suggest that LinfCul1 regulates the S phase progression and possibly the transition between the late S to G2 phase in L. infantum. Thus, a new class of E3 ubiquitin ligases has been described in L. infantum with functions related to various parasitic processes that may serve as prospective targets for leishmaniasis treatment.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionDepartment of Genetics and Evolution Federal University of São Carlos-
Descrição: dc.descriptionDepartment of Biochemistry and Immunology Ribeirão Preto Medical School University of São Paulo-
Descrição: dc.descriptionInstitute of Infection Immunity and Inflammation University of Glasgow-
Descrição: dc.descriptionDepartment of Biochemistry Institute of Chemistry University of São Paulo-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Biosciences Institute São Paulo State University (UNESP)-
Descrição: dc.descriptionSao Carlos Institute of Physics University of São Paulo, Sao Carlos-
Descrição: dc.descriptionDepartment of Animal Biology Institute of Biology University of Campinas-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Biosciences Institute São Paulo State University (UNESP)-
Descrição: dc.descriptionFAPESP: 2015/26722-8-
Descrição: dc.descriptionFAPESP: 2016/20258-0-
Descrição: dc.descriptionFAPESP: 2016/21171-6-
Descrição: dc.descriptionFAPESP: 2019/10753-2-
Descrição: dc.descriptionFAPESP: 2022/00923-0-
Descrição: dc.descriptionFAPESP: 2023/07193-0-
Idioma: dc.languageen-
Relação: dc.relationPLoS Pathogens-
???dc.source???: dc.sourceScopus-
Título: dc.titleFunctional characterization of Cullin-1-RING ubiquitin ligase (CRL1) complex in Leishmania infantum-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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