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Evaluation of the proteolytic processing of TGFB citokyne in melanoma secretomes

Grant number: 19/10817-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2019
Effective date (End): September 30, 2020
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:André Zelanis Palitot Pereira
Grantee:Uilla Barcick de Souza
Home Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
Associated scholarship(s):19/24805-4 - Recombinant production of TGFb cytokine for the analysis of its proteolytic processing, BE.EP.IC

Abstract

The search for cancer biomarkers is a field in which a large amount of human and financial resources are concentrated, both from private and public research around the world. Experimental approaches in proteomics related to the prospection of biomarkers aim to find specific proteins, characteristic expression patterns, or markers of tumor progression. In a recent study on the proteolytic processing of a paired set of murine melanoma composed of the Melan-a (a normal melanocyte) and Tm1 (the corresponding tumor phenotype) cell lines, it was possible to identify, exclusively in the tumor phenotype, proteolytic processing events in proteins of important role in tumor development. Among the cleavage sites observed, we identified a peptide corresponding to the processing of the TGF²-3 precursor protein in a portion immediately prior to the canonical cleavage site for this cytokine. From the functional point of view, this finding suggests a non-canonical and autocrine activation of TGF²-3 by transformed melanocytes. Thus, this project has as main objective to identify processed forms of the cytokine TGFb in the secretomes and cell lysates of tumor melanocytes, correlating the results obtained with possible secretory/processing pathways of this cytokine.