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Table 1 Functions of mammalian Nek kinases

From: Nek family of kinases in cell cycle, checkpoint control and cancer

ID Functions Disease associations Cancer Mutations
Nek1 -excess catalytic activity leads to loss of primary cilia (IMCD3 cells) [45]
-Nek1-/- cells display defective G1/S and G2/M checkpoints and DNA repair after IR [64]
-mutation is causal in Kat, Kat2J mouse models of PKD [37]
-mutation identified as causal in 2 families with autosomal-recessive short-rib polydactyly syndrome [42]
tumor samples:
ovarian (C191F, K779N)
large intestinal (N181N*)
lung (E25K)
cultured cells:
lung (A294P)
Nek2 -promotes centrosome splitting at G2/M and chromosome segregation [15, 16, 73, 15, 16, 21]
-regulates chromosome segregation [73]
-catalytic activity inhibited following IR, preventing centrosome separation [62]
-elevated expression in: colangiocarcinoma tumors [74, 75]
- elevated expression in MDA-MB-231 and MCF7 cells; knockdown suppresses proliferation in vitro and tumor burden of xenografts in vivo [75]
tumor samples:
breast (R115Q, E278K)
stomach (G134D)
Nek3 -regulates microtubule deacetylation in neurons [30]
-regulates prolactin-mediated cytoskeleton rearrangement and motility of T47D breast cancer cells [84]
  tumor samples:
ovarian (D413Y)
cultured cells:
stomach(Y398**)
Nek4 - knockdown alters sensitivity of MCF7 cells to microtubule poisons taxol and vincristine [31]   tumor samples:
large intestinal (R777K)
Nek5 -uncharacterized   tumor samples:
mouth (K201**)
Nek6 -required for mitotic spindle formation and cytokinesis [26]
-promotes centrosome separation [27]
-activated downstream of Nek9 [85]
-overexpressed in a variety of human tumors [77]
-knockdown inhibits HeLa xenografts [77]
-Nek6 expression downregulated following p53-induced senescence [78]
tumor samples:
ovarian (Y295C, Y291Y*)
cultured cells:
kidney (I99S)
Nek7 -required for mitotic spindle formation and cytokinesis [26]
-promotes centrosome separation [27]
-activated downstream of Nek9 [85]
-rare Nek7-/- mice survive to birth and exhibit severe growth retardation [28] tumor samples:
lung (G7**)
ovarian (I275M)
cultured cells:
stomach (M8L, V285I)
Nek8 -regulation of primary cilia; regulates localization and expression of ciliary proteins PC-1, PC-2 [40, 43] -mutation is causal in Jck mouse model of PKD [36]
-overexpressed in primary human breast tumors [86]
tumor samples:
liver (G605D)
ovarian (P703***)
stomach (R292Q)
cultured cells:
pancreatic (A197P)
skin (L621F)
stomach (L341P)
Nek9 -regulation of primary cilia; regulates localization and expression of ciliary proteins PC-1, PC-2 [40, 43]   tumor samples:
ovarian (V319***)
cultured cells:
lung (P870S)
stomach (V631I, R786Q)
Nek10 - regulates establishment of UV-induced G2/M checkpoint [66]
- interacts with Raf-1/MEK1 to promote MEK1 autoactivation following UV irradiation [66]
-GWAS identified Nek10 as a strong breast cancer susceptibility locus [80]
- various mutations identified in primary tumours and cancer cells lines [82]
tumor samples:
ovarian (V319***)
cultured cells:
lung (P870S)
stomach (V631I, R786Q)
Nek11 -required for G2/M arrest following IR [55]
-activated by Chk1 phosphorylation
-phosphorylates DSG motif of Cdc25A leading to its ubiquitination and degradation [55]
  tumor samples:
ovarian (A66V, V568I, D875Y, F50L, S852S*),
lung (R878M)
brain (I783V, S797S*)
cultured cells:
skin (E379K)
  1. Nek kinase somatic mutations in tumor samples and cultured cells as catalogued in the COSMIC database (Sanger Institute/Wellcome Trust). (*) silent mutations; (**) nonsense mutations; (***) deletion-frameshift mutations.