1 n otherwise identical fibroblasts expressing
Nek1.
2 cribed sequences from this region identified
Nek1,
a NIMA (never in mitosis A)-related kinase as a ca
3 acterized the dynamic protein interactome of
NEK1 after DNA damage challenge with cisplatin.
4 identification of heterozygous mutations in
NEK1 and DYNC2H1 in an additional family.
5 e replicated known ALS genes including SOD1,
NEK1 and FUS.
6 Our data suggest that
NEK1 and its interaction partners trigger the DNA damage
7 activation relies on the kinase activity of
Nek1 and its interaction with ATR-ATRIP.
8 d ubiquitination and that the interaction of
Nek1 and TAZ maintain PC2 at the level needed for proper
9 drome Majewski type to identify mutations in
NEK1 as an underlying cause of this lethal osteochondrod
10 ated with ALS (MATR3, CHCHD10, TBK1, TUBA4A,
NEK1,
C21orf2, and CCNF), all of which were identified b
11 These data suggest that TAZ and
Nek1 constitute a negative feedback loop linked through
12 -function variants in NIMA-related kinase 1 (
NEK1)
constitute a major genetic cause of amyotrophic la
13 Nek1 deficiency as well as expression of unphosphorylata
14 NEK1 deficiency disrupts endosomal trafficking of plasma
15 The metabolic and proteomic defects of
NEK1 deficiency disrupts the integrity of blood-brain ba
16 revent postnatal lethality and BBB damage in
NEK1 deficient mice.
17 aggregation of a-synuclein in the brains of
NEK1 deficient mice.
18 Finally,
Nek1-
deficient fibroblasts are much more sensitive to th
19 with two distinct classes of drugs restored
NEK1-
dependent deficits in both pathways.
20 ectrometry analyses for NEK1 interactors and
NEK1-
dependent expression changes, we find functional en
21 NEK1 encodes a serine/threonine kinase with proposed fun
22 Thus, as an ATR-associated kinase,
Nek1,
enhances the stability and activity of ATR-ATRIP b
23 activity is increased within 4 minutes, and
Nek1 expression is up-regulated shortly thereafter and s
24 Upon DNA damage, cells lacking
Nek1 failed to efficiently phosphorylate multiple ATR su
25 Furthermore, TAZ targets
Nek1 for degradation.
26 Further analysis of the
Nek1 gene from both kat/kat and kat(2J)/kat(2J) mutant a
27 Loss-of-function mutations in
NEK1 gene, which encodes a serine/threonine kinase, are
28 NEK1 has been linked to several cellular functions, incl
29 Never-in-mitosis A-related kinase 1 (
Nek1)
has established roles in apoptosis and cell cycle
30 NIMA-related kinase 1 (
Nek1)
has lately garnered attention for its widespread f
31 nctions of the NimA-related mammalian kinase
Nek1 have not been demonstrated to date.
32 the structure of the kinase domain of human
NEK1 in its apo- and ATP-mimetic inhibitor bound forms.
33 s identify a previously unsuspected role for
Nek1 in the kidney and open a new avenue for studying cy
34 ed in these processes, are phosphorylated by
NEK1 in vitro.
35 uted tubules, supporting our hypothesis that
Nek1-
inhibition causes cystic kidneys in zebrafish embry
36 ure-guided design of a potent small-molecule
Nek1 inhibitor, starting from a scaffold identified by k
37 Using mass spectrometry analyses for
NEK1 interactors and NEK1-dependent expression changes,
38 NEK1 is essential for motor control and survival in Dros
39 NEK1 is essential for the ionizing radiation DNA damage
40 induced by ionizing radiation (IR) and that
Nek1 is important for cells to repair and recover from D
41 Here we show that
Nek1 is involved early in the DNA damage response induce
42 NEK1 is likely to be essential for mitosis in asexual bl
43 Importantly, even in undamaged cells,
Nek1 is required for maintaining the levels of ATRIP, th
44 (never in mitosis A)-related kinase family,
Nek1,
is critical for initiating the ATR response.
45 mary or transformed cells are exposed to IR,
Nek1 kinase activity is increased within 4 minutes, and
46 These data suggest that P. berghei
NEK1 kinase is an important component of MTOC organisati
47 nd activation, both of which are reversed by
NEK1 kinase-mediated S336 phosphorylation.
48 potent stem cell (iPSC)-MN models, including
NEK1 knockdown, kinase inhibition, and a patient mutatio
49 Loss of
Nek1 leads to underphosphorylation of TAZ, thereby promo
50 Here, we study
NEK1 location and function, using live cell imaging, ult
51 We report spatiotemporal
NEK1 location in real-time, coordinated with microtubule
52 th p.Arg261His (10,589 samples analyzed) and
NEK1 LOF variants (3,362 samples analyzed).
53 HR and rescues the HR defect associated with
Nek1 loss.
54 These results suggest that
Nek1 may function as a kinase early in the DNA damage re
55 However, how
NEK1 mutations cause motor neuron (MN) dysfunction is un
56 ers of the NimA-related kinase (NEK) family (
NEK1,
NEK10, and NEK11) in the DDR.
57 Unlike
Nek1-
Nek9, Nek10 is a dual-specificity kinase that effic
58 (ZRANB3 [OMIM 615655], PCGF3 [OMIM 617543],
NEK1 [
OMIM 604588], NUPL2, GALC [OMIM 606890], and CTSB
59 s found, most commonly in SOD1, TARDBP, FUS,
NEK1,
OPTN or TBK1.
60 ed community in the Netherlands identified a
NEK1 p.Arg261His variant as a candidate risk factor.
61 report that the nimA-related protein kinase
Nek1 phosphorylates TAZ at a site essential for the ubiq
62 hus, G2-specific phosphorylation of Rad54 by
Nek1 promotes Rad51 chromatin removal during HR in G2 ph
63 e homozygous mutant animals suggest that the
NEK1 protein participates in different signaling pathway
64 its kinase activity is highest, a portion of
Nek1 redistributes in cells from cytoplasm to discrete n
65 We show that human
Nek1 regulates homologous recombination (HR) by phosphor
66 In summary,
Nek1 regulates Rad51 removal to orchestrate HR and repli
67 Here we show that
NEK1 regulates retromer-mediated endosomal trafficking b
68 In total, we observed
NEK1 risk variants in nearly 3% of ALS cases.
69 found that absence of functional full-length
NEK1 severely reduces cilia number and alters ciliar mor
70 NEK1 shows pleiotropic functions and has been found to b
71 s risk regions of ALS genes, including SOD1,
NEK1,
TARDBP, and FUS While not clearly implicating nove
72 y of axonemal microtubules through targeting
Nek1,
the ciliary kinase, for proteolysis.
73 Knockdown studies reveal
NEK1 to be an essential component of the MTOC in male ce
74 The capacity of
NEK1 to modulate these processes that are critically inv
75 The ability of
Nek1 to promote ATR activation relies on the kinase acti
76 at inhibiting the set of four kinases AURKB,
NEK1,
TTK, and WEE1 causes simulated HeLa cells to accum
77 t association between loss-of-function (LOF)
NEK1 variants and FALS risk.