NEK5 phosphoproteomic profiling: identification of phospho-substrates in cancer cells and validation of known targets

• Grant number: 19/11435-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): September 16, 2019
• Effective date (End): September 15, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Camila de Castro Ferezin
• Supervisor: Roger Daly
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: Monash University, Australia
• Associated to the scholarship: 16/10530-5 - The funtion of the protein kinase Nek5 in normal and cancer cells: from the identification of physiological substrates to inhibitor design, BP.DD

Abstract

NEKs (Nima Related Kinases) family is one of poorest characterized mitotic kinases family and plays important roles not only in the cell cycle but also in DNA Damage Response and other functions apart from the cell cycle such as regulation of cytosolic and mitochondrial proteins, regulation of apoptosis and autophagy. Therefore, these kinases have the potential to become important therapeutic targets for a range of diseases, especially cancer. Of the 11 members of the NEK family, NEK5 is one of the least characterized kinases, both structurally and functionally. Recent publications have pointed to the involvement of NEK5 with poor prognosis and tumor progression in breast cancer and to its up-regulation in prostate cancer. To be better understand the role of NEK family members in cancer, we purpose to perform a kinomic screening of cancer cells lines and evaluate the phosphoproteomic profile of the NEK kinases. We also intend to identify interaction networks and pathways associated with NEK kinases through the integration of the data and bioinformatic analysis. Moreover, we intend to perform targeted approaches to deeper understand some of the kinases signalings and what are the outcomes that modulations (such as inhibition) may cause. We believe that the purposed project might provide valuable information about NEK5 - and other NEKs - roles in cancer cells and might be a first step into the studies of NEK family as therapeutical targets. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FEREZIN, CAMILA DE CASTRO; SIAN, TERRY C. C. LIM KAM; WU, YUNJIAN; MA, XIUQUAN; CHUEEH, ANDERLY C.; HUANG, CHENG; SCHITTENHELM, RALF B.; KOBARG, JORG; DALY, ROGER J.. Identification of biological pathways and processes regulated by NEK5 in breast epithelial cells via an integrated proteomic approach. CELL COMMUNICATION AND SIGNALING, v. 20, n. 1, p. 15-pg., 2022-12-22. (16/10530-5, 19/11435-4, 17/03489-1)