Ricerc@Sapienza

Biological processes, metabolism, cell growth and differentiation, apoptosis and angiogenesis are controlled by reversible phosphorylation of proteins.
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 and/or removal of the phosphate group may affect the function of the protein target by modifying its structure, stability, substrate or ligand affinity, and activity. Dysregulation of the protein kinases signaling is observed in many diseases like cardiovascular and neurodegenerative diseases or in immunological disorders, in diabetes and cancer. MAPK3 (ERK1) is a component of the complex MAPK signaling 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 MAPK3 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 MAPK3 expressed in cancer tissues and reported in cancer databases. These variants will be characterized to investigate the effect of a single amino acid substitution on MAPK3 activity, thermal and thermodynamic stability and structure in solution.