Analysis of the role of Nek10 in mitochondria

• Grant number: 20/07006-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2020
• End date: April 30, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Andressa Peres de Oliveira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/03489-1 - From functional studies to searching for new inhibitors for cancer: exploring kinases that regulate the cell cycle of the human NEK family, AP.TEM
• Associated scholarship(s): 21/07071-7 - Study of the regulation of scaffolding protein ATAD3 of the inner mitochondrial membrane by human NEK10 kinase: impact on mitochondrial metabolism and morphology, BE.EP.PD

Abstract

1983 Oakley and Morris identified, in a genetic cell division screen, in the filamentous fungus Aspergillus nidulans, a protein kinase named NIMA (Never In Mitosis gene A), founding member of the NEK family kinases (NIMA related kinases). The NEKs were identified in a vast spectrum of organisms, from protozoans to multicellular eukaryonts, including Drosophila, Xenopus, mice and humans. Humans possess 11 genes that encode proteins NEK1-11. One of the least studied family member is Nek10. Mutations in Nek10 were related to Breast Cancer. This protein has its catalytic domain flanked by two extensive regulatory domains. At the N-terminus we have four armadillo motifs for protein interactions. Moniz and Stambolic demonstrated in 2011 that NEK10 is involved in the G2/M checkpoint after UV light exposure of cells. Nek10 acts as a positive regulator of ER1/2 after UV light exposure through formation of a RAF1 and MEK1 complex. Recently another study demonstrated the importance of Nek10 in ciliogenesis and embryogenesis in vertebrates, where Nek10 interacts with PKA and PCM1 and participates in the signaling pathway of cAMP. Mitochondria are organelles with a double membrane and their own genome. They are involved in energy productin, Ca2+ homeostasis , cell death regulation, cellular aging and chronic inflammation. Alterations in mitochondrial homeostasis contribute to metabolic syndromes , heart diseases , neurodegeneration and Cancer. Recently, some interacting proteins/substrates were related to NEKs that are involved in mitochondrial functions. Nek1 regulates cell death via phosphorylation of VDAC1. Cells silenced for expression of Nek5 show increased levels of ROS formation and cell death. Nek2 has an important role in anerobic glycolysis, regulates PKM processing and increases the ration of PKM2/PKM1 in myeloma cells. (AU)