Study of dimerization and signaling mechanisms of the mutant IL7Ra

• Grant number: 12/07992-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2012
• End date: December 06, 2017
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: José Andrés Yunes
• Grantee: Lívia Weijenborg Campos
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil
• Associated scholarship(s): 15/23611-0 - Mechanism of activation of the cystein-mutant and wild type IL7R receptors, BE.EP.DR

Abstract

The acute lymphoid leukemias (ALL) are widely associated with chromosomal abnormalities and recurrent genetic mutations. A recent study describes the occurrence of mutations in exon 6 of the IL-7 receptor (IL7Ra) alpha chain gene in 9% of the T phenotype ALL (ALL-T). In most cases (80%), IL7Ra mutations resulted in insertion of a cysteine in the extracellular portion juxtaposed to the transmembrane receptor domain. The "mutant" cysteine contributes to the unusual formation of homodimers/oligomers of IL7Ra, constitutive signaling via JAK1/STAT5 and induction of cell survival and proliferation, typical of oncogenic mutations. The present project aims to better detail the mechanism of dimerization and subcellular localization of mutant IL7R signaling. Effect of cystein mutagenesis (insertions and deletions) on IL7R dimers/oligomers formation and signaling strength will be analyzed. Since homodimers/oligomers can be formed already in the endoplasmic reticulum, attempts will be made to better describe the IL7R dimerization/oligomerization in this cell compartment. A better understanding of the structure and function, of mutant IL-7R may help define ways of inhibiting its oncogenic action.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CAMPOS, Lívia Weijenborg. Study on the mutant IL7RA mechanisms of dimerization and signaling. 2019. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.