NEK5, short for NIMA Related Kinase 5, is a member of the Never-in-mitosis kinase family. It has been shown to regulate centrosome integrity in somatic cells, and is involved in cell cycle progression, mitochondrial functions, and DNA damage response [3,4,5,6]. Its malfunction may be associated with cancer development, especially breast cancer [1,2,7]. Genetic models, such as gene knockout (KO) mouse models, can be valuable tools to study its functions.

In breast cancer, knockdown of NEK5 significantly suppresses cell proliferation both in vivo and in vitro, and inhibits migration and invasion. NEK5 can up-regulate Cyclin A2 and down-regulate Cyclin D1, D3, and E1 expression, and Cyclin A2 is a novel interacting protein for NEK5 [1]. Also, NEK5 activation in breast cancer cells promotes cell migration independent of cell proliferation, and its overexpression or knockdown affects metastatic potential in a cell type-specific manner [2]. In mouse oocytes, Nek5 depletion significantly increases the phosphorylation level of cyclin-dependent kinase 1, decreases maturation-promoting factor activity, and impairs germinal vesicle breakdown and preimplantation embryonic development [3]. Moreover, NEK5-silenced cells are more sensitive to etoposide treatment, as NEK5 depletion increases DNA damage and impairs proper DNA damage response [4]. And in mitochondria, NEK5 interacts with LonP1, and its kinase activity is essential for maintaining mitochondrial mass, functionality, and mtDNA integrity after oxidative damage [5].

In conclusion, NEK5 plays crucial roles in multiple biological processes, including cell cycle regulation during oocyte maturation and preimplantation embryonic development, DNA damage response, and mitochondrial homeostasis. In the context of breast cancer, studies using loss-of-function models have revealed its oncogenic role in promoting cell proliferation and metastasis, suggesting it could be a potential therapeutic target [1,2,3,4,5].

References:

1. Pei, Jing, Zhang, Jing, Yang, Xiaowei, Wang, Zhaorui, Wang, Benzhong. 2019. NEK5 promotes breast cancer cell proliferation through up-regulation of Cyclin A2. In Molecular carcinogenesis, 58, 933-943. doi:10.1002/mc.22982. https://pubmed.ncbi.nlm.nih.gov/30675923/

2. Matossian, Margarite D, Elliott, Steven, Van Hoang, T, Collins-Burow, Bridgette M, Burow, Matthew E. 2021. NEK5 activity regulates the mesenchymal and migratory phenotype in breast cancer cells. In Breast cancer research and treatment, 189, 49-61. doi:10.1007/s10549-021-06295-4. https://pubmed.ncbi.nlm.nih.gov/34196902/

3. Li, Yuan-Yuan, Guo, Lei, Li, Hui, Lu, Sheng-Sheng, Han, Zhiming. 2019. NEK5 regulates cell cycle progression during mouse oocyte maturation and preimplantation embryonic development. In Molecular reproduction and development, 86, 1189-1198. doi:10.1002/mrd.23234. https://pubmed.ncbi.nlm.nih.gov/31304658/

4. Melo-Hanchuk, Talita Diniz, Slepicka, Priscila Ferreira, Pelegrini, Alessandra Luiza, Menck, Carlos Frederico Martins, Kobarg, Jörg. 2019. NEK5 interacts with topoisomerase IIβ and is involved in the DNA damage response induced by etoposide. In Journal of cellular biochemistry, 120, 16853-16866. doi:10.1002/jcb.28943. https://pubmed.ncbi.nlm.nih.gov/31090963/

5. Ferezin, Camila de Castro, Basei, Fernanda Luisa, Melo-Hanchuk, Talita D, de Souza-Pinto, Nadja C, Kobarg, Jörg. 2021. NEK5 interacts with LonP1 and its kinase activity is essential for the regulation of mitochondrial functions and mtDNA maintenance. In FEBS open bio, 11, 546-563. doi:10.1002/2211-5463.13108. https://pubmed.ncbi.nlm.nih.gov/33547867/

6. Prosser, Suzanna L, Sahota, Navdeep K, Pelletier, Laurence, Morrison, Ciaran G, Fry, Andrew M. . Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis. In The Journal of cell biology, 209, 339-48. doi:10.1083/jcb.201412099. https://pubmed.ncbi.nlm.nih.gov/25963817/

7. de Castro Ferezin, Camila, Lim Kam Sian, Terry C C, Wu, Yunjian, Kobarg, Jörg, Daly, Roger J. 2022. Identification of biological pathways and processes regulated by NEK5 in breast epithelial cells via an integrated proteomic approach. In Cell communication and signaling : CCS, 20, 197. doi:10.1186/s12964-022-01006-y. https://pubmed.ncbi.nlm.nih.gov/36550548/