Functional Analysis of Human Nima-Related Kinase 8 (Nek8)

Abstract

Nek8 is a member of NIMA-related kinase family (Nrk) and contains an N-terminal serine/threonine kinase domain highly homologous with that of NIMA. Most of the NIMA-related kinase family members are involved in cell cycle regulation. However, roles of Nek8 in cell cycle and cellular regulation are largely unknown. Herein, I identified two novel binding partners of Nek8: a small GTPase Ran and a chaperon protein Hsp70. Ran can interact with Nek8 and facilitate the shuffling of Nek8 between cytoplasm and nucleus, which indicates Nek8 may involve in the nuclear transport process. Furthermore, Nek8 was found to be localized in endoplasmic reticulum (ER). Overexpression of Nek8 in cells could delay apoptosis induced by the ER stress drugs, which indicate that Nek8 may be responsible for protecting cells from ER stress-induced apoptosis. Nek8 has been reported to be linked with some diseases, such as cancer and kidney disease. Mutation in Nek8 gene could cause the polycystic kidney disease (PKD), which suggested a function of hNek8 in ciliogenesis. However the detailed mechanism of this disease is not clear. Our observation of Nek8¿s role to protect cells from apoptosis induced by ER stress could provide a new direction for study on Nek8 in the kidney disease and cancers.