Human Nek4: connecting DNA damage response and cell death

• Grant number: 13/11018-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2013
• End date: November 30, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Fernanda Luisa Basei
• Supervisor: Joan Roig Amorós
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Institution abroad: Institute for Research in Biomedicine (IRB), Spain
• Associated to the scholarship: 09/14221-3 - Characterization of the two human signaling proteins Nek 11 and Nek 4 - a biochemical and functional approach, BP.DR

Abstract

Neks are serine/threonine kinases related to NIMA, their orthologue from Aspergillus nidulans. Eleven human Neks have been identified (1-11) and there is growing evidence pointing Neks role in diverse cellular process, such as cell cycle control, including cell division, mitotic spindle assembly, furrow ingression, primary cilium formation and maintenance, besides DNA damage response and apoptosis control. Nek1 is the best characterized Nek in DNA damage response, playing an important role in ATR/ATRIP repair pathway in response to double strand break induced by ionizing radiation (IR). Nek11 also is important to this process in the same pathway, but indirectly, through cell cycle control after DNA damage. In addition to DNA damage response, Nek1 is also activated in mitochondria after cell damage through VDAC phosphorylation and inhibition of cytochrome c release. In agreement with literature data for Nek1 and Nek11, Nek4 interaction with others proteins which participate in non-homologue end joining (NHEJ) pathway repair have been already demonstrated. Besides, recently we have obtained results indicating Nek4 involvement in reactive oxygen species (ROS) response and Nek4 mitochondrial localization. In addition, new Nek4 interacting partners involved in DNA damage response and cell death were found in our studies. In view of this, the aim of this project is to shed light on Nek4 role in DNA repair pathways, cell cycle control and cell death. (AU)