Nek8, a serine-threonine kinase that regulates the cell cycle: functional studies of mutations found in human colon cancer

• Grant number: 23/15911-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Kauany de Oliveira Ferreira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/15126-9 - Two cell cycle regulatroy protein families: from functional studies to their use as novel diagnostic markers and therapeutic targets in cancer, AP.TEM
• Associated scholarship(s): 24/22038-4 - Characterization of the Nek8 protein interactome using Proximity-dependent Biotin Identification (BioID), BE.EP.MS

Abstract

In general, Neks (NIMA-related kinases) are a family of serine/threonine/tyrosinekinases that regulate the cell cycle of eukaryotic cells. Neks consist of enzymesconsidered relevant targets in several pathologies, including cancer. From datacarried out by the Pan American Health Organization (PAHO/WHO) in 2020, colorectal cancer isconsidered one of the most lethal. This work will have as main objective to analyze the changesfunctional functions of NEK8 knockout colon cancer cells, overexpressing full length NEK8 andWT kinase domain and with the mutations found in colon cancer available in the databasedata from the COSMIC platform. Based on data generated by the group, it was identified that the mutationG149S (sigmoid colon adenocarcinoma) there is a change in electrophoretic mobility with reduction ofCDK2 and tendency towards reduction of ³H2AX, increase in acetylated Tubulin and reduction in Beta-Cateninwhen compared to cells transfected with empty-FLAG, the kinase domain of NEK8 WT and theE195K mutation, with this set of data being indicative of the mutation causing greater activation of theNEK8. Thus, there may be mutants associated with activation and inactivation found intumors, especially colon cancer, and future studies are essential to improveunderstanding, development of possible inhibitors and more accurate diagnoses.