Exploring the function of TIPRL in cellular models of PP2A biogenesis

• Grant number: 18/09337-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 01, 2018
• End date: July 26, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Juliana Helena Costa Smetana
• Grantee: Ana Amélia Sanchez Iacia
• Supervisor: Egon Ogris
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Institution abroad: Medical University of Vienna, Austria
• Associated to the scholarship: 16/12560-9 - Functional characterization of the role of regulatory protein TIPRL in normal and cancer cells, BP.DR

Abstract

PP2A (protein phosphatase 2A), a conserved phosphoserine/-threonine specific phosphatase, is a major regulator of several cellular processes, including cell cycle, signal transduction, autophagy and metabolism. It counteracts the activation of mitogenic pathways by dephosphorylating key signaling molecules, thereby acting as an important tumor suppressor. The functional unit of PP2A is a heterotrimeric holoenzyme composed of a globular catalytic subunit (PP2Ac or C subunit), a scaffold subunit (PR65/A), and a structurally diverse range of regulatory subunits (B, B', B', B'''). The catalytic subunit is activated and assembled into holoenzymes by a series of regulated steps involving inhibitor proteins, chaperones and post-translational modifications of its conserved C-terminal tail, a process termed as PP2A biogenesis. Our group has previously solved the crystal structure of TIPRL, which is a protein inhibitor of PP2A, and which binds specifically to the C-terminal tail of PP2Ac, both of which suggest a role of TIPRL in PP2A biogenesis. The major objective of this project is to use validated tools and the expertise of the Ogris laboratory to analyze the role of TIPRL in PP2A biogenesis. These include a collection of cell lines stably expressing PP2Ac mutants, and a series of phenotypic readouts of the Neuro2a cell line which are directly related with PP2A biogenesis. (AU)