NEK7

Fig1. Schematic model of Nek7 activation by Nek9 binding and induced dimerization. Phosphorylation of Nek7 by Nek9 kinase activity is an alternative mechanism in vivo. (Tamanna Haq, 2015)

What is NEK7 protein?

NEK7 (NIMA related kinase 7) gene is a protein coding gene which situated on the long arm of chromosome 1 at locus 1q31. NEK7 is a member of the NIMA family of serine/threonine kinases. There are 11 members of the family (NEK1-NEK11), of which NEK7 is the youngest. NEK7 is expressed in a variety of tissues and plays an important role in the mitotic phase of the cell cycle. In contrast to the other documented NIMA-related kinases, NEK7 harbor its catalytic domain in the C-terminus of the protein. NEK7 is highly expressed in lung, muscle, testis, brain, heart, liver, leukocyte and spleen. The NEK7 protein is consisted of 302 amino acids and its molecular mass is approximately 34.6 kDa.

What is the function of NEK7 protein?

NEK7 is a protein kinase which plays an important role in mitotic cell cycle progression and it is required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis. NEK7 kinase activity is rapidly and efficiently increased by serum deprivation, and may be regulated in a cell cycle-dependent manner. Also, it serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division: interaction with NEK9 prevents interaction with NLRP3 and activation of the inflammasome during mitosis.

Fig2. NEK7 targets at NLRP3 and involves in the activation of NLRP3 inflammasome. (Jin Xu, 2016)

NEK7 Related Signaling Pathway

It is mainly involved in the following signaling pathways and cellular processes: NLRP3 inflammasome activation, NEK7 directly binds to NLRP3 and promotes the assembly and activation of inflammasome; NEK7 plays a role in the mitotic phase of the cell cycle, particularly during spindle assembly, centrosome separation, and chromosome separation. NEK7 regulates these events by phosphorylating substrates, ensuring proper cell division; NEK7 is also involved in regulating mitochondrial morphology and function, including mitochondrial fission and fusion, as well as maintaining mitochondrial homeostasis.

NEK7 Related Diseases

NEK7 plays a role in the Inflammatory response and has been linked to inflammatory diseases such as Rheumatoid arthritis and Inflammatory bowel disease. Studies have shown that NEK7 may be involved in the occurrence and development of these diseases by regulating the activation of the NLRP3 inflammasome and cytokine release. NEK7 may be involved in neurodegenerative diseases by regulating mechanisms such as inflammatory response and mitochondrial function. At the same time, it can also participate in the development of cancer by regulating the cell cycle, such as breast cancer, lung cancer, colorectal cancer and so on.

Bioapplications of NEK7

Although NEK7 is a potential drug target, no specific inhibitor is currently validated or approved for clinical treatment. The current research on NEK7 as a potential drug target is in the early stages, and some natural products and chemical synthetic compounds may have an inhibitory effect on NEK7.

Case study 1: Akshari Gupta, 2017

The decision to commit to the cell cycle is made during G1 through the concerted action of various cyclin-CDK complexes. Not only DNA replication, but also centriole duplication is initiated as cells enter the S-phase. The NIMA-related kinase NEK7 is one of many factors required for proper centriole duplication, as well as for timely cell cycle progression. However, its specific roles in these events are poorly understood.

In this study, NEK7 acts at least before the restriction point during G1 by depleting this gene in human U2OS cells. Using multiple experimental means including Immunofluorescence, Immunoblotting to verify the NEK7 related mechanism: depletion of NEK7 inhibits progression through the G1 phase in human U2OS cells via down-regulation of various cyclins and CDKs and also inhibits the earliest stages of procentriole formation.

Fig1. Total cell lysates were analyzed by immunoblotting using antibodies against the indicated proteins at least twice.

Fig2. Depletion of NEK7 induces ciliogenesis. Total cell lysates in each condition were analyzed by immunoblotting against the indicated antibodies.

Case study 2: Lei Zhou, 2016

NEK7 is a serine/threonine kinase involved in cell-cycle progression via mitotic spindle formation and cytokinesis. But whether Nek7 involves in hepatocellular carcinoma (HCC) and what is NEK7's role in HCC are unknown. In this study, the researchers measured the expressiong of NEK7 in HCC and liver tissues. In addition, by Nek7 silencing using lentivirus-mediated Nek7 interference approach, HCC cell lines and xenograft mouse model were obtained.

The results shows that Nek7 was significantly overexpressed in HCC than in liver tissues. Furthermore, Nek7 expression pattern showed close relationship with that of Ki-67, a well-stablished cell proliferation marker. More importantly, patients with higher expression levels of Nek7 had significantly lower 5-years survival rate. And in vitro, the growth of HCC cell lines was inhibited and the tumor growth in xenograft mouse model was also suppressed. Thus, Nek7 would be a useful biomarker that early predicts HCC patients at higher risk of poor prognosis. Also, Nek7 could be a novel HCC therapeutic target.

Fig3. The results of Nek7 mRNA and protein expression in tissue specimens and cell lines.

Fig4. HepG2 C cells were infected with lenti-shNek7-1, -2 and negative control lenti-shNC.

NEK7 has several biochemical functions, for example, ATP binding,metal ion binding,protein serine/threonine kinase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by NEK7 itself. We selected most functions NEK7 had, and list some proteins which have the same functions with NEK7. You can find most of the proteins on our site.

NEK7 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with NEK7 here. Most of them are supplied by our site. Hope this information will be useful for your research of NEK7.

NEK9;NEK6;q7ard3_yerpe;Nek9