Identification of glutaminase interacting partners and functional studies

• Grant number: 11/21863-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2012
• End date: May 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sandra Martha Gomes Dias
• Grantee: Marcel Nakahira
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated research grant: 09/10875-9 - Cellular and biochemical studies of the glutaminase enzyme and its relation with cancer, AP.JP

Abstract

One of the most important goals in cancer research is the identification of the molecular changes that drives normal cells to evolve into malignant tumors. Cancer cells undergo marked changes in their metabolic activity in order to sustain the malignant phenotype. One such set of changes is the increased glucose uptake, the up-regulation of several glycolytic enzymes, as well as isoform selection toward more efficient enzymes. All this culminates with the intensification of the glycolytic pathway, a phenomenon known as Warburg effect. The increased glycolysis, one of the hallmarks of cancer, brings bioenergetic and biosynthetic advantages to the neoplasic cells. A direct result of this is the higher dependence of cells on the aminoacid glutamine, essential to support their biosynthetic platform. Protein interaction networks are essential for controlling intracellular signaling events, to control protein activity, and also to diversify protein function. The glutaminase (GLS), a key enzyme in the glutamine metabolism, presents, besides its catalytic domain, others domains or motifs notably known to be involved in protein-protein interactions. This project aims to identify the importance of the three glutaminase isoenzymes (kidney-type glutaminase, glutaminase C e liver-type glutaminase) for the tumoral process by means of determining its interacting partners using the yeast two-hybrid system. Initial studies of the liver-type glutaminase have identified three proteins as potential partners which will be explored to understand their importance for the enzyme subcellular localization.