Ricerc@Sapienza

Reversible phosphorylation of proteins controls most of biological processes, such as metabolism, cell growth and differentiation, apoptosis and angiogenesis. Protein kinases catalyze the transfer of a phosphate group from ATP or GTP to the hydroxyl group of either a serine, threonine, or tyrosine protein residue, and protein phosphatases remove the phosphate group. Addition of the phosphate group, or its removal, may affect the function of the protein target by modifying its structure, stability, substrate or ligand affinity, and activity. Dysregulation of the protein kinases signalling is observed in many diseases like cardiovascular and neurodegenerative diseases or in immunological disorders, in diabetes and cancer. ERK1 (MAPK3) is a component of the complex MAPK signalling involved in oncogenesis, tumor progression and drug resistance. In cancer tissues has been reported the expressions of several somatic non synonymous single nucleotide variants (nsSNVs) of ERK1 carrying a single amino acid substitution in the sequence. A single amino acid substitution can potentially affect the protein structure-function relationships in different ways, such as changes in protein function, stability, flexibility and interaction with other proteins, nucleic acids, or drugs and other molecules. The aim of this project is the selection of some natural nsSNVs of ERK1 expressed in cancer tissues and reported in cancer databases. These variants will be characterized to investigate the effect of single amino acid substitution on ERK1 activity, thermal and thermodynamic stability and structure in solution.