NEK7

Official Full Name

NIMA related kinase 7

Organism

Homo sapiens

GeneID

140609

Background

NIMA-related kinases share high amino acid sequence identity with the gene product of the Aspergillus nidulans 'never in mitosis A' gene, which controls initiation of mitosis.[supplied by OMIM, Jul 2002]

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Detailed Information

NIMA-related kinase 7, Nek7, is an important part of the activation of NLRP3 inflammatory bodies. Nek7 is widely present in eukaryotic cells and is one of the smallest members found in the NEK family. Nek7, located at both levels of the spindle, consists almost entirely of catalytic kinase domains with two amino-terminal kinase regions and no carboxy terminus. Nek6 and Nek7 have the same catalytic domain of 85%. The mitotic regulatory factor Polo-like kinase 1 (Plk1) and cyclin dependent kinase 1 (CDK1) activate Nek9, making it directly Combine Nek6 and Nek7 to control cytokinesis.

On the other hand, Nek7 is involved in the activation of NLRP3 inflammatory bodies as part of the NLRP3 inflammatory complex. Inactive NLRP3 inflammatory bodies are induced by the NF-κB pathway, and under the coordination of ROS pathway, K+ efflux, lysosomal disruption and Nek7, the inactive NLRP3 inflammatory body aggregates and activates, eventually leading to IL -1β, IL-18 maturation and secretion. By blocking the secretion of IL1β, IL-18 and binding to its receptor, it is possible to control and alleviate the progression of inflammatory diseases. Therefore, Nek7 may become a new target for the treatment of various inflammatory diseases.

Figure 1. Nek7 interacts and stabilizes TRF1 at telomeres upon oxidative damage. (Tan, R., et al. 2017)

Nek7 and Mitosis

Located in the centrosome, Nek7 is one of the 11 NEK kinases found in vertebrates and is one of the smallest members of the conserved non-mitosis Aspergillus (NIMA)-related family members. It is widely expressed in various tissues such as brain, heart, lung, liver, spleen and kidney. As a multi-functional protein kinase, Nek7 regulates proteins involved in biological processes. It is a highly conserved serine/threonine kinase (Nek) essential for mammalian survival, cellular changes, and mitosis. The role of the mitotic kinase Nek in cell mitosis is similar to that of NIMA. The regulation of key members of the N2 family members involved in G2/M phase during mitosis promotes centrosome maturation and affects chromatin concentration and spindle formation.

Nek7 Involved in the Activation of NLRP3 Inflammatory Bodies

Under normal growth conditions, Nek7 is in a low activity state, which is the key to maintaining the stability of the internal environment. However, in the pathological state, the homeostasis is destroyed, Nek7 is overexpressed, and multinucleated cells and apoptotic cells closely related to inflammation are produced in large quantities, eventually leading to the occurrence of inflammatory reactions in the body. Studies have shown that Nek7 is an important regulatory substance required for the activation of NLRP3 inflammatory bodies. In the downstream reaction of NLRP3 activation, Nek7 binds to the leucine rich repeat (LRR) in NLRP3 in an independent kinase manner, thereby further mediating the activation of NLRP3 inflammatory bodies, which cause an inflammatory response. Experiments have shown that Nek7 has a key function of reducing the dynamic stability of microtubules during the in vitro interval and phosphorylation of α-tubulin and β-tubulin, with microtubule acetylation and NLRP3 inflammatory body signaling. In the same way, in the cells knocked out of Nek7, alpha-tubulin acetylation increased, indicating that Nek7 is involved in microtubule acetylation during activation of NLRP3 inflammatory bodies.

References:

Eduardo, M. , Gabriela, M. , Rodrigo, H. , Tatiana, D. S. , Edmarcia, D. S. , & Mario, M. , et al. (2015). Kinase inhibitor profile for human nek1, nek6, and nek7 and analysis of the structural basis for inhibitor specificity. Molecules, 20(1), 1176-1191.
He, Y. , Zeng, M. Y. , Yang, D. , Motro, B. , & Gabriel Núñez. (2016). Nek7 is an essential mediator of nlrp3 activation downstream of potassium efflux. Nature, 530(7590), 354-357.
Tan, R. , Nakajima, S. , Wang, Q. , Sun, H. , Xue, J. , & Wu, J. , et al. (2017). Nek7 protects telomeres from oxidative dna damage by phosphorylation and stabilization of trf1. Molecular Cell, 65(5), 818-831.e5.

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