Proteomic profiling of the proteolytic events in the secretome of the transformed phenotype of melanocyte-derived cells using Terminal Amine Isotopic Labeling of Substrates

Autor(es)

Liberato, Tarcisio ^[1] ; Fukushima, Isabella ^[1] ; Kitano, Eduardo S. ^{[2, 3]} ; Serrano, Solange M. T. ^[2] ; Chammas, Roger ^[4] ; Zelanis, Andre ^[1]

Afiliação do(s) autor(es)

^[1] Fed Univ Sao Paulo ICT UNIFESP, Dept Sci & Technol, Funct Prote Lab, Sao Jose Dos Campos, SP - Brazil

^[2] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Lab Especial Toxinol Aplicada, Sao Paulo - Brazil

^[3] Inst Butantan, Ctr Excellence New Target Discovery CENTD, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PROTEOMICS; v. 192, p. 291-298, FEB 10 2019.
• Citações Web of Science: 1

Resumo

The comprehensive profiling of the repertoire of secreted proteins from cancer cells samples provides information on the signaling events in oncogenesis as well as on the cross-talk between normal and tumoral cells. Moreover, the analysis of post-translational modifications in secreted proteins may unravel biological circuits regulated by irreversible modifications such as proteolytic processing. In this context, we used Terminal Amine Isotopic Labeling of Substrates (TAILS) to perform a system-wide investigation on the N-terminome of the secretomes derived from a paired set of mouse cell lines: Melan-a (a normal melanocyte) and Tm1 (its transformed phenotype). Evaluation of the amino acid identities at the scissile bond in internal peptides revealed significant differences, suggesting distinct proteolytic processes acting in the normal and tumoral secretomes. The mapping and annotation of cleavage sites in the tumoral secretome suggested functional roles of active proteases in central biological processes related to oncogenesis, such as the processing of growth factors, cleavage of extracellular matrix proteins and the shedding of ectopic domains from the cell surface, some of which may represent novel processed forms of the corresponding proteins. In the context of the tumor microenvironment, these results suggest important biological roles of proteolytic processing in murine melanoma secreted proteins. (AU)

• Processo FAPESP: 14/06579-3 - Análise sistêmica do processamento N-terminal e diversidade de proteínas no secretoma de células tumorais
• Beneficiário: André Zelanis Palitot Pereira
• Linha de fomento: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/18096-0 - Otimização de técnicas de enriquecimento nterminal para análise proteômica em larga escala de amostras complexas
• Beneficiário: Isabella Fukushima
• Linha de fomento: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 17/07897-7 - Análise do processamento proteolítico no secretoma de células tumorais de melanoma
• Beneficiário: Isabella Fukushima
• Linha de fomento: Bolsas no Brasil - Iniciação Científica