Affinage

NEK6

Serine/threonine-protein kinase Nek6 · UniProt Q9HC98

Length
313 aa
Mass
35.7 kDa
Annotated
2026-06-10
64 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NEK6 is a serine/threonine kinase that functions as a terminal effector of a mitotic kinase cascade in which PLK1/CDK1 activate NEK9, and NEK9 in turn directly phosphorylates NEK6 on its activation-loop residue Ser206 to drive a 20-25-fold increase in NEK6 activity (PMID:12840024, PMID:21642957). Activated NEK6 is required for progression through mitosis: its loss or inhibition produces metaphase arrest with fragile spindles followed by apoptosis (PMID:14563848, PMID:19414596). Mechanistically, NEK6 localizes to spindle microtubules and the midbody and phosphorylates a set of mitotic substrates to build a functional bipolar spindle — Eg5/KIF11 at Ser1033 to promote centrosome separation (PMID:19001501, PMID:21642957), Hsp72 at Thr66 to target it to spindle poles and recruit the ch-TOG/TACC3 complex for K-fiber assembly (PMID:25940345), and EML4 at Ser144/146 to release EML4 from mitotic microtubules and permit chromosome congression (PMID:31409757). The same cascade promotes centrosome clustering into pseudo-bipolar spindles in cells with amplified centrosomes (PMID:28720575). NEK6 activity is restrained during DNA damage, when Chk1 and Chk2 directly phosphorylate NEK6 to block its mitotic activation, and the cascade is further tuned by DYNLL/LC8, which competes with NEK6 for binding to NEK9 (PMID:21454704, PMID:18728393). Beyond mitosis, NEK6 acts as a regulator of transcription-factor localization and stability in diverse settings: it phosphorylates and activates STAT3 at Ser727 (PMID:20595392, PMID:34643969), phosphorylates FOXO3 (Ser7) and FOXN3 (Ser412/416) to control their nuclear access and downstream ubiquitination programs (PMID:39256367, PMID:39984467), phosphorylates YBX1 (Ser102) to drive its nuclear translocation (PMID:41560755), and stimulates LSD1 demethylase activity at chromatin sub-compartments (PMID:39523439). Through these activities NEK6 modulates p53-induced senescence, TGFβ/Smad signaling, telomere regulation via TPP1, and chemoresistance (PMID:21099361, PMID:27396482, PMID:25523445, PMID:39256367). A single residue (Gln132 in NEK6 versus Arg121 in NEK7) explains why NEK6, unlike its paralog NEK7, does not support NLRP3 inflammasome activation (PMID:35354613).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Established NEK6 as a bona fide protein kinase by purifying it biochemically as a major activity phosphorylating the p70 S6 kinase hydrophobic-motif site, giving the first candidate substrate.

    Evidence Biochemical purification from rat liver plus in vitro kinase assay and dominant-negative expression

    PMID:11516946

    Open questions at the time
    • Physiological relevance of S6K phosphorylation by NEK6 not yet resolved at this stage
    • No cellular role defined
  2. 2002 High

    Defined NEK6 substrate specificity (Leu at -3) and showed by mutagenesis that NEK6 is NOT the physiological insulin/IGF-1-induced hydrophobic-motif kinase for S6K/SGK/PKB, redirecting the search for its true biological function.

    Evidence Peptide-library kinetic analysis and mutant substrate phosphorylation in IGF-1-stimulated cells

    PMID:12023960

    Open questions at the time
    • Left NEK6's authentic in vivo substrates unidentified
    • No connection to a cellular process yet
  3. 2003 High

    Placed NEK6 in a defined activation cascade by demonstrating direct NEK9 phosphorylation of NEK6 at activation-loop Ser206, and independently showed NEK6 is required for mitotic progression.

    Evidence In vitro reconstitution with recombinant proteins, MS phosphosite mapping, and siRNA/dominant-negative phenotyping with time-lapse microscopy

    PMID:12840024 PMID:14563848

    Open questions at the time
    • Mitotic substrates of NEK6 still unknown
    • Upstream activator of NEK9 not yet defined
  4. 2008 High

    Identified the first mitotic substrate (Eg5 at Ser1033) and showed NEK6 is checkpoint-regulated, revealing both its effector function and how it is suppressed during DNA damage.

    Evidence Co-IP, in vitro kinase assays, phosphospecific antibodies, Eg5 mutant rescue; separately Chk1/Chk2 in vitro phosphorylation of NEK6 from irradiated cells

    PMID:18728393 PMID:19001501

    Open questions at the time
    • Eg5-Ser1033-Ala only partially impaired, implying additional substrates
    • Chk1/Chk2 phosphosites on NEK6 and mechanism of inhibition not mapped (Medium confidence for checkpoint arm)
  5. 2009 High

    Distinguished NEK6 from its paralog NEK7 functionally, showing non-redundant localization (spindle MTs/midbody vs spindle poles) and separate requirements for spindle formation and cytokinesis.

    Evidence Reciprocal siRNA depletion, dominant-negative expression, and immunofluorescence localization

    PMID:19414596

    Open questions at the time
    • Molecular basis of distinct localization not defined
    • Midbody substrate(s) unidentified
  6. 2011 High

    Completed the upstream wiring (PLK1→NEK9→NEK6/7→Eg5) and defined LC8/DYNLL as a competitive brake on the cascade, plus provided a low-resolution structural picture implicating the disordered N-terminus in partner binding.

    Evidence Kinase assays, sequential depletion/rescue epistasis, phosphosite mutagenesis, LC8 binding-motif mutagenesis; SAXS/SEC-MALS/CD for NEK6 architecture

    PMID:21320329 PMID:21454704 PMID:21642957

    Open questions at the time
    • High-resolution NEK6 structure absent
    • Functional role of N-terminal disorder not validated by mutagenesis
  7. 2015 High

    Elucidated how NEK6 builds K-fibers by phosphorylating Hsp72 at Thr66 to recruit the ch-TOG/TACC3 module, and extended NEK6 into non-mitotic signaling (TGFβ/Smad4, GBP-1/chemoresistance).

    Evidence In vitro kinase assay with phosphomimetic rescue and substrate-complex Co-IP for Hsp72; Co-IP/reporter assays for Smad4; far-western for GBP-1

    PMID:25523445 PMID:25940345 PMID:26269749

    Open questions at the time
    • GBP-1 interaction rests on a single method (Low confidence)
    • Direct Smad4 phosphorylation by NEK6 not demonstrated
  8. 2017 Medium

    Connected NEK6/Hsp72 to centrosome clustering, showing a context-specific (amplified-centrosome) vulnerability where NEK6 loss forces multipolar spindles.

    Evidence siRNA depletion and phosphospecific immunofluorescence in cancer vs normal cells

    PMID:28720575

    Open questions at the time
    • Limited mechanistic detail on the clustering step
    • No quantitative substrate-level analysis
  9. 2019 High

    Provided structural-mechanistic understanding of how NEK6 (with NEK7) controls microtubule dynamics by phosphorylating EML4 at Ser144/146 to release it from the microtubule lattice, enabling chromosome congression.

    Evidence In vitro kinase assay, microtubule sedimentation, cryo-EM reconstruction of the binding interface, and phosphosite mutant analysis

    PMID:31409757

    Open questions at the time
    • Relative NEK6 vs NEK7 contribution at this substrate not separated
    • Timing/spatial control of EML4 phosphorylation in vivo not fully resolved
  10. 2022 High

    Defined the single-residue determinant (NEK6 Gln132 vs NEK7 Arg121) explaining NEK6's inability to bind NLRP3, and uncovered a mitochondrial/redox-homeostasis role through CRISPR knockout phenotypes.

    Evidence Point-mutant Co-IP and inflammasome assays in macrophages; CRISPR knockout with respiration, ROS, and antioxidant-protein readouts in prostate cancer cells

    PMID:35354613 PMID:36672191

    Open questions at the time
    • Direct mitochondrial substrate of NEK6 unidentified
    • Mechanism linking NEK6 to antioxidant defense and NF-κB2 not defined
  11. 2025 Medium

    Consolidated NEK6 as a phosphorylation switch governing transcription-factor localization and stability across disease contexts — FOXO3 (Ser7), FOXN3 (Ser412/416), YBX1 (Ser102), STAT3, and LSD1 — linking it to chemoresistance, fibrosis, reactive astrogliosis, and tumor proliferation.

    Evidence Co-IP, in vitro/in-cell kinase assays with defined phosphosites, ChIP, ubiquitination assays, phase-separation assays, and xenograft/animal models across multiple studies

    PMID:34643969 PMID:39256367 PMID:39523439 PMID:39984467 PMID:41560755

    Open questions at the time
    • Each transcription-factor substrate validated by single labs
    • How mitotic and transcriptional NEK6 pools are spatially/temporally segregated is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single activation-loop-regulated kinase coordinates its many spatially distinct substrate pools (spindle, centrosome, nucleus, mitochondria) and what governs substrate selection in each compartment.
  • No high-resolution structure of active NEK6 with substrate
  • No systematic in vivo substrate map distinguishing mitotic from interphase targets
  • Compartment-specific activation/scaffolding mechanisms undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 5 GO:0140657 ATP-dependent activity 1
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 2 GO:0005815 microtubule organizing center 2 GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-73894 DNA Repair 1
Partners
DYNLL1EML4FOXO3KIF11NEK9PIN1SMAD4STAT3

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 NEK9/Nercc1 directly phosphorylates NEK6 at Ser206 on its activation loop in vitro, causing 20-25-fold activation of NEK6 kinase activity; this phosphorylation also occurs in vivo during mitosis and is stimulated by co-expression with activated NEK9 mutant, establishing a NEK9→NEK6 mitotic kinase cascade. In vitro kinase assay with recombinant proteins, co-expression of activated NEK9 mutant with NEK6 in cells, mass spectrometry phosphosite identification The Journal of biological chemistry High 12840024
2001 NEK6 (and NEK7) were purified from rat liver as the major kinase activity phosphorylating the p70 S6 kinase hydrophobic motif site Thr412; recombinant NEK6 phosphorylates p70 S6K at Thr412 and activates it in vitro and in vivo synergistically with PDK1; kinase-inactive NEK6 interferes with insulin-induced p70 S6K activation. Biochemical purification from rat liver, in vitro kinase assay, co-expression/dominant-negative in cells Current biology : CB High 11516946
2002 NEK6 has a strong substrate specificity preference for Leu at the -3 position relative to the phosphorylation site; mutation of this Leu in S6K1 or SGK1 prevents their in vitro phosphorylation by NEK6, but these mutants are still phosphorylated at the hydrophobic motif in cells after IGF-1 stimulation, indicating NEK6 is NOT responsible for insulin/IGF-1-induced hydrophobic motif phosphorylation of S6K, SGK, or PKB in vivo. Peptide library (Jerini pepSTAR) kinetic analysis, in vitro phosphorylation of mutant S6K1/SGK1, transfected 293 cells with IGF-1 stimulation The Journal of biological chemistry High 12023960
2003 NEK6 is required for cell cycle progression through mitosis in human cells; inhibition of NEK6 by kinase-inactive mutant or siRNA causes metaphase arrest prior to apoptosis, as shown by time-lapse microscopy. siRNA knockdown, dominant-negative kinase-inactive mutant overexpression, time-lapse microscopy The Journal of biological chemistry High 14563848
2008 NEK6 is constitutively associated with Eg5 (KIF11/Kinesin-5) and phosphorylates Eg5 at Ser1033 in vivo during mitosis primarily at spindle poles; this phosphorylation is required for full mitotic function of Eg5, as Eg5[Ser1033Ala] rescues only ~50% of cells depleted of Eg5 compared to wild-type, while a phosphomimetic Ser1033Asp rescues nearly as well as wild-type. Co-immunoprecipitation, in vitro kinase assay, phosphospecific antibody, rescue experiments with Eg5 point mutants in RNAi-depleted cells Journal of cell science High 19001501
2009 NEK6 and NEK7 are both required for robust mitotic spindle formation and cytokinesis; depletion of either causes metaphase arrest with fragile spindles and apoptosis; NEK6 specifically localizes to spindle microtubules in metaphase/anaphase and to the midbody during cytokinesis, while NEK7 shows only spindle pole localization, demonstrating their non-redundant roles. siRNA depletion, dominant-negative mutant expression, antibody localization/immunofluorescence, SAC inhibitor combination experiments Molecular and cellular biology High 19414596
2011 PLK1 is identified as a direct activator of NEK9, which in turn activates NEK6/7; PLK1 controls prophase centrosome separation through NEK9 activation and subsequent NEK6/7-dependent phosphorylation of kinesin Eg5 at Ser1033, and the CDK1 site Thr926 together contribute to Eg5 centrosome accumulation and centrosome separation. Co-immunoprecipitation, kinase assays, phosphospecific antibodies, siRNA depletion, rescue experiments The EMBO journal High 21642957
2011 DYNLL/LC8 binds to the Nek9 C-terminal region via a (K/R)XTQT motif, causing Nek9 multimerization and accelerating Nek9 autoactivation; LC8 binding to Nek9 is negatively regulated by Nek9 autophosphorylation at Ser944; LC8 binding also competitively interferes with Nek9-Nek6 interaction and Nek6 activation, acting as a regulatory brake on the Nek9→Nek6 cascade. Co-immunoprecipitation, in vitro kinase assays, mutagenesis of Nek9 phosphosite and binding motif The Journal of biological chemistry High 21454704
2010 NEK6 interacts with STAT3 and phosphorylates STAT3 at Ser727, which is important for transcriptional activation; both Ser206 and Thr210 phosphorylation of NEK6 itself are required for this activity and for anchorage-independent transformation; NEK6 knockdown reduces colony formation and STAT3 Ser727 phosphorylation. Co-immunoprecipitation, in vitro kinase assay, NEK6 phosphosite mutants, siRNA knockdown, anchorage-independent growth assay The Journal of biological chemistry Medium 20595392
2008 NEK6 is phosphorylated upon IR and UV irradiation through the DNA damage checkpoint; Chk1 and Chk2 directly phosphorylate NEK6 in vitro; DNA damage abolishes NEK6 activation during mitosis; ectopic NEK6 overexpression overrides DNA damage-induced G2/M arrest, placing NEK6 downstream of the checkpoint kinases as a required effector. In vitro kinase assay with Chk1/Chk2, immunoprecipitation-kinase assay from irradiated cells, overexpression studies Cell cycle (Georgetown, Tex.) Medium 18728393
2015 NEK6 phosphorylates Hsp72 at Thr66 within its nucleotide-binding domain, targeting it to the mitotic spindle; phosphorylated Hsp72 concentrates at spindle poles and kinetochore-microtubule attachment sites; Hsp72 promotes K-fiber assembly by facilitating ch-TOG and TACC3 interaction and their recruitment to spindle MTs; a phosphomimetic Hsp72 (T66D) rescues K-fiber defects, ch-TOG/TACC3 recruitment defects, and mitotic arrest caused by NEK6 depletion. In vitro kinase assay, phosphospecific antibody, siRNA depletion, phosphomimetic rescue, co-immunoprecipitation, immunofluorescence The Journal of cell biology High 25940345
2011 Human NEK6 is a monomeric, mostly globular kinase with a flexible, disordered N-terminal domain; SAXS reveals slightly elongated shape in solution; phosphorylation state affects NEK6 conformation (higher phosphorylation increases Stokes radius); the disordered N-terminal domain mediates interactions with diverse partners. SAXS, SEC-MALS, circular dichroism, homology modeling, thermal shift assay BMC structural biology Medium 21320329
2010 NEK6 overexpression suppresses p53-induced senescence in a kinase-activity-dependent manner; kinase-dead NEK6 does not affect p53-induced senescence; NEK6 overexpression reduces cell cycle arrest in G1/G2M, maintains cyclin B and cdc2 levels, and inhibits ROS increases induced by p53. NEK6 overexpression and kinase-dead mutant in cancer cell lines, flow cytometry, Western blot for cyclin B/cdc2 Cell cycle (Georgetown, Tex.) Medium 21099361
2016 NEK6 phosphorylates TPP1 (shelterin component) at Ser255 during G2/M phase; this phosphorylation regulates the association between telomerase activity and TPP1; POT1 negatively regulates TPP1 Ser255 phosphorylation; NEK6-TPP1 interaction was detected in human cells. Co-immunoprecipitation, phosphospecific antibody for TPP1 Ser255, cell synchronization, telomerase activity assay Genes to cells : devoted to molecular & cellular mechanisms Medium 27396482
2019 NEK6 and NEK7 phosphorylate EML4 at Ser144 and Ser146 within its basic N-terminal domain; these phosphorylations reduce EML4 affinity for the acidic C-terminal tails of α/β-tubulin on the microtubule surface; depletion of NEK6/7 increases EML4-microtubule binding in mitosis; EML4 S144A-S146A double mutant binds inappropriately to mitotic microtubules, stabilizes them, and impairs chromosome congression. In vitro kinase assay, microtubule sedimentation assay, cryo-EM 3D reconstruction, depletion by siRNA, EML4 phosphosite mutant analysis Science signaling High 31409757
2017 NEK6 and its upstream activators PLK1 and Aurora-A target Hsp72 to the poles of cells with amplified centrosomes, promoting centrosome clustering into pseudo-bipolar spindles; blocking Hsp72 or NEK6 triggers multipolar spindle formation only in cells with amplified centrosomes, not in normal cells. siRNA depletion, phosphospecific antibodies, immunofluorescence in cancer cells with amplified centrosomes vs. normal cells Cancer research Medium 28720575
2015 NEK6 directly interacts with GBP-1, making NEK6 a component of the cytoskeletal gateway of drug resistance; NEK6 expression is induced by hypoxia in a HIF-1α-dependent manner in ovarian cancer cells. Far western blot for NEK6-GBP1 interaction, hypoxia treatment, HIF-1α silencing, overexpression/silencing of NEK6 American journal of cancer research Low 26269749
2006 Pin1 (peptidyl-prolyl isomerase) interacts with NEK6, as confirmed by GST pull-down and co-immunoprecipitation and immunofluorescence colocalization in cells. GST pull-down, co-immunoprecipitation, immunofluorescence colocalization Biochemical and biophysical research communications Low 16476580
2015 NEK6 interacts with Smad4 and over-expression of NEK6 suppresses TGFβ-mediated transcriptional activity in a kinase activity-dependent manner; NEK6 blocks nuclear translocation of Smad4 and suppresses TGFβ-induced cell growth arrest; NEK6 expression is itself regulated by TGFβ and hypoxia. Co-immunoprecipitation, reporter assay for TGFβ transcriptional activity, subcellular fractionation for Smad4 localization, kinase-dead NEK6 mutant BMB reports Medium 25523445
2020 miR-325-3p upregulation after M. tuberculosis infection directly targets LNX1 (an E3 ubiquitin ligase of NEK6), reducing LNX1-mediated proteasomal degradation of NEK6; accumulated NEK6 activates STAT3 signaling, inhibiting macrophage apoptosis and promoting intracellular M. tuberculosis survival. miRNA target validation, LNX1 as E3 ligase for NEK6 demonstrated, STAT3 signaling readout, Mir325-deficient mice, macrophage cell and mouse models mBio Medium 32487755
2016 Phosphoproteome profiling identified transcription factor FOXJ2 as a novel NEK6 substrate in the context of castration resistance; NEK6 overexpression stimulates cytoskeletal, differentiation, and immune signaling gene expression programs. Phosphoproteome profiling, gene expression profiling, kinome screen Cancer research Low 27899381
2021 NEK6 associates with and phosphorylates STAT3; NEK6 kinase activity is required for induction of GFAP and PCNA (markers of reactive astrogliosis); NEK6 is also localized in the nucleus and binds to STAT3-responsive genomic elements in astrocytes; NEK6 expression is rapidly induced after brain injury and promotes reactive astrogliosis. Co-immunoprecipitation, kinase assay, ChIP (binding to STAT3 genomic elements), immunofluorescence, loss-of-function/gain-of-function in astrocytes Glia Medium 34643969
2024 NEK6 directly interacts with FOXO3 and phosphorylates it at Ser7 through kinase activity, inhibiting FOXO3 nuclear translocation; nuclear FOXO3 promotes FBXW7 transcription leading to c-MYC ubiquitination and suppression of de novo purine synthesis; NEK6-mediated inhibition of this pathway supports chemoresistance in ovarian cancer. Co-immunoprecipitation, in vitro/in vivo kinase assay for FOXO3-S7 phosphorylation, subcellular fractionation, reporter assay, xenograft model Cell death & disease Medium 39256367
2025 NEK6 phosphorylates FOXN3 at Ser412 and Ser416 in response to pro-fibrotic stimuli, leading to FOXN3 degradation; loss of FOXN3 inhibits β-TrCP-mediated ubiquitination of Smad4, stabilizing the Smad2/3/4 complex at chromatin and promoting transcriptional activation of pro-fibrotic genes, contributing to pulmonary fibrosis. In vitro kinase assay, phosphosite mutagenesis, co-immunoprecipitation, ChIP, ubiquitination assay, loss-of-function in cell and animal models Nature communications High 39984467
2022 A single amino acid residue distinguishes NEK6 from NEK7 in NLRP3 inflammasome activation: NEK7 Arg121 (vs NEK6 Gln132) mediates NLRP3 binding; substituting Gln132 with Arg in NEK6 confers NEK6 the ability to bind NLRP3 and activate the inflammasome in mouse macrophages; NEK6 does NOT support NLRP3 inflammasome activation under normal conditions. Point mutant co-immunoprecipitation, inflammasome activation assay in macrophages, mutagenesis Journal of immunology (Baltimore, Md. : 1950) High 35354613
2024 NEK6 kinase stimulates LSD1 histone demethylase activity in cells; NEK6 phosphorylates LSD1 at the N-terminal intrinsically disordered region (IDR); NEK6 and LSD1 strongly colocalize at distinct chromatin sub-compartments (CSCs); LSD1 IDR shows phase separation behavior in vitro and in cells, and NEK6-mediated phosphorylation promotes LSD1 concentration at CSCs, supporting dynamic transcriptional control. Co-localization/co-immunoprecipitation, in vitro and in-cell kinase assay for LSD1 phosphorylation, phase separation assay, chromatin fractionation Communications biology Medium 39523439
2025 NEK6 binds to YBX1 in the cytoplasm and phosphorylates it at Ser102, promoting YBX1 nuclear translocation; nuclear YBX1 activates CDK2 and BCL2 transcription; NEK6 and CDK4/6 inhibition are synthetically lethal in endometrial cancer. Co-immunoprecipitation, phosphospecific assay, nuclear fractionation, CRISPR-Cas9 screen, in vitro and in vivo tumor models Frontiers in pharmacology Medium 41560755
2022 NEK6 knockout in DU-145 prostate cancer cells reduces mitochondrial respiration, causes mitochondrial fragmentation (reduced cristae), increases intracellular ROS, decreases antioxidant proteins (SOD1, SOD2, PRDX3), increases JNK phosphorylation and DNA damage markers, and reduces NF-κB2 nuclear localization; NEK6 overexpression increases antioxidant defenses. CRISPR-Cas9 knockout, Western blot, ROS assay, mitochondrial respiration assay, clonogenic assay Cells Medium 36672191
2026 NEK6 knockout in DU-145 prostate cancer cells causes mitochondrial morphological defects (fragmented phenotype with reduced cristae), reduced mitochondrial respiration, increased autophagic flux targeting mitochondria (mitophagy), altered fusion/fission regulators (decreased Long-OPA1:Short-OPA1 ratio and DRP1), and increased ER-mitochondria contacts. CRISPR-Cas9 knockout, transmission electron microscopy, Western blot, mitochondrial respiration assay, autophagy flux assay Cells Medium 42193938
2025 NEK6 binds TCP10L and promotes its ubiquitination and degradation; TCP10L negatively regulates glycolysis in hepatocellular carcinoma; NEK6-mediated TCP10L downregulation accelerates HCC proliferation, metastasis, and glycolysis. Co-immunoprecipitation, ubiquitination assay, Western blot, siRNA knockdown rescue experiments Critical reviews in eukaryotic gene expression Low 40228222

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases. The Journal of biological chemistry 154 12840024
2011 Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. The EMBO journal 150 21642957
2009 The Nek6 and Nek7 protein kinases are required for robust mitotic spindle formation and cytokinesis. Molecular and cellular biology 142 19414596
2008 The NIMA-family kinase Nek6 phosphorylates the kinesin Eg5 at a novel site necessary for mitotic spindle formation. Journal of cell science 120 19001501
2018 Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway. Cancer biology & therapy 96 30207869
2003 The serine/threonine kinase Nek6 is required for cell cycle progression through mitosis. The Journal of biological chemistry 94 14563848
2002 Molecular basis for the substrate specificity of NIMA-related kinase-6 (NEK6). Evidence that NEK6 does not phosphorylate the hydrophobic motif of ribosomal S6 protein kinase and serum- and glucocorticoid-induced protein kinase in vivo. The Journal of biological chemistry 80 12023960
2001 Identification of the NIMA family kinases NEK6/7 as regulators of the p70 ribosomal S6 kinase. Current biology : CB 71 11516946
2010 Nek6 overexpression antagonizes p53-induced senescence in human cancer cells. Cell cycle (Georgetown, Tex.) 61 21099361
2010 Nek6 mediates human cancer cell transformation and is a potential cancer therapeutic target. Molecular cancer research : MCR 60 20407017
2000 Isolation and characterization of two evolutionarily conserved murine kinases (Nek6 and nek7) related to the fungal mitotic regulator, NIMA. Genomics 54 10964517
2008 Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-induced phosphorylation. Cell cycle (Georgetown, Tex.) 51 18728393
2020 MicroRNA-325-3p Facilitates Immune Escape of Mycobacterium tuberculosis through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling. mBio 46 32487755
2015 Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression. The Journal of cell biology 43 25940345
2014 gga-miR-26a targets NEK6 and suppresses Marek's disease lymphoma cell proliferation. Poultry science 43 24795301
2010 Role of NEK6 in tumor promoter-induced transformation in JB6 C141 mouse skin epidermal cells. The Journal of biological chemistry 43 20595392
2014 Characterization of the human NEK7 interactome suggests catalytic and regulatory properties distinct from those of NEK6. Journal of proteome research 39 25093993
2019 Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity of EML4 to promote chromosome congression. Science signaling 38 31409757
2006 Interaction of Pin1 with Nek6 and characterization of their expression correlation in Chinese hepatocellular carcinoma patients. Biochemical and biophysical research communications 37 16476580
2016 Castration Resistance in Prostate Cancer Is Mediated by the Kinase NEK6. Cancer research 33 27899381
2015 Nek6 and Hif-1α cooperate with the cytoskeletal gateway of drug resistance to drive outcome in serous ovarian cancer. American journal of cancer research 31 26269749
2018 Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6. Scientific reports 30 30375481
2011 Clinical and biological significance of never in mitosis gene A-related kinase 6 (NEK6) expression in hepatic cell cancer. Pathology oncology research : POR 30 21725899
2015 The potential role of the NEK6, AURKA, AURKB, and PAK1 genes in adenomatous colorectal polyps and colorectal adenocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 29 26423403
2019 Retraction: MiR-506-3p inhibits cell proliferation, induces cell cycle arrest and apoptosis in retinoblastoma by directly targeting NEK6 by Lina Wu, Zhen Chen, Yiqiao Xing. Cell biology international 28 30080301
2025 Phosphorylation of FOXN3 by NEK6 promotes pulmonary fibrosis through Smad signaling. Nature communications 27 39984467
2017 Hsp72 and Nek6 Cooperate to Cluster Amplified Centrosomes in Cancer Cells. Cancer research 27 28720575
2003 Differential control of the NIMA-related kinases, Nek6 and Nek7, by serum stimulation. Biochemical and biophysical research communications 26 12589797
2002 The related murine kinases, Nek6 and Nek7, display distinct patterns of expression. Mechanisms of development 25 11744387
2015 Kinase inhibitor profile for human nek1, nek6, and nek7 and analysis of the structural basis for inhibitor specificity. Molecules (Basel, Switzerland) 24 25591119
2015 An inhibitory role of NEK6 in TGFβ/Smad signaling pathway. BMB reports 23 25523445
2011 Human Nek6 is a monomeric mostly globular kinase with an unfolded short N-terminal domain. BMC structural biology 23 21320329
2011 DYNLL/LC8 protein controls signal transduction through the Nek9/Nek6 signaling module by regulating Nek6 binding to Nek9. The Journal of biological chemistry 23 21454704
2002 Identification and characterization of Nek6 protein kinase, a potential human homolog of NIMA histone H3 kinase. Biochemical and biophysical research communications 23 12054534
2022 CRISPR/Cas9 screen in human iPSC-derived cortical neurons identifies NEK6 as a novel disease modifier of C9orf72 poly(PR) toxicity. Alzheimer's & dementia : the journal of the Alzheimer's Association 22 35993441
2011 Nek6 suppresses the premature senescence of human cancer cells induced by camptothecin and doxorubicin treatment. Biochemical and biophysical research communications 22 21539811
2021 Knockdown of circ_NEK6 Decreased 131I Resistance of Differentiated Thyroid Carcinoma via Regulating miR-370-3p/MYH9 Axis. Technology in cancer research & treatment 21 33759638
2013 The inhibition of Nek6 function sensitizes human cancer cells to premature senescence upon serum reduction or anticancer drug treatment. Cancer letters 21 23416273
2024 NEK6 dampens FOXO3 nuclear translocation to stabilize C-MYC and promotes subsequent de novo purine synthesis to support ovarian cancer chemoresistance. Cell death & disease 18 39256367
2017 Directional cell expansion requires NIMA-related kinase 6 (NEK6)-mediated cortical microtubule destabilization. Scientific reports 17 28798328
2022 miR-141-3p suppresses development of clear cell renal cell carcinoma by regulating NEK6. Anti-cancer drugs 16 34387594
2012 Aurora kinase A (AURKA) and never in mitosis gene A-related kinase 6 (NEK6) genes are upregulated in erosive esophagitis and esophageal adenocarcinoma. Experimental and therapeutic medicine 15 23060919
2023 NEK6 Regulates Redox Balance and DNA Damage Response in DU-145 Prostate Cancer Cells. Cells 14 36672191
2016 NEK6-mediated phosphorylation of human TPP1 regulates telomere length through telomerase recruitment. Genes to cells : devoted to molecular & cellular mechanisms 14 27396482
2020 microRNA-219-5p targets NEK6 to inhibit hepatocellular carcinoma progression. American journal of translational research 13 33312387
2017 cis-Regulatory Circuits Regulating NEK6 Kinase Overexpression in Transformed B Cells Are Super-Enhancer Independent. Cell reports 13 28329684
2021 NEK6 is an injury-responsive kinase cooperating with STAT3 in regulation of reactive astrogliosis. Glia 12 34643969
2021 Circular RNA NEK6 contributes to the development of non-small-cell lung cancer by competitively binding with miR-382-5p to elevate BCAS2 expression at post-transcriptional level. BMC pulmonary medicine 12 34663267
2014 Discovery of novel inhibitors for Nek6 protein through homology model assisted structure based virtual screening and molecular docking approaches. TheScientificWorldJournal 12 24587765
2022 NIMA-related kinase-6 (NEK6) as an executable target in cancer. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 11 36074296
2022 LncRNA FAM13A-AS1 Promotes Renal Carcinoma Tumorigenesis Through Sponging miR-141-3p to Upregulate NEK6 Expression. Frontiers in molecular biosciences 10 35402517
2022 MicroRNA-323a-3p Negatively Regulates NEK6 in Colon Adenocarcinoma Cells. Journal of oncology 9 35096064
2024 Nek6 regulates autophagy through the mTOR signaling pathway to alleviate cerebral ischemia-reperfusion injury. Molecular brain 8 39702325
2022 A Single Amino Acid Residue Defines the Difference in NLRP3 Inflammasome Activation between NEK7 and NEK6. Journal of immunology (Baltimore, Md. : 1950) 8 35354613
2015 [Expression of NEK-6 in gastric cancer and its clinical significance]. Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 7 26499152
2023 NEK6 Promotes the Progression of Osteosarcoma Through Activating STAT3 Signaling Pathway by Down-Regulation of miR-26a-5p. International journal of general medicine 6 37426517
2023 Nek6 knockdown polarized macrophages into a pro-inflammatory phenotype via inhibiting STAT3 expression. International journal of experimental pathology 5 37431082
2025 NEK6 Accelerates Hepatocellular Carcinoma Progression and Glycolysis through Ubiquitination of TCP10L. Critical reviews in eukaryotic gene expression 3 40228222
2025 NEK6 functions as an oncogene to promote the proliferation and metastasis of ovarian cancer. Journal of Cancer 1 39895790
2024 The kinase NEK6 positively regulates LSD1 activity and accumulation in local chromatin sub-compartments. Communications biology 1 39523439
2026 Genome-wide CRISPR screen identified NEK6 as a determinant of sensitivity to CDK4/6 inhibitor in endometrial cancer. Frontiers in pharmacology 0 41560755
2026 Integrating single-cell and spatial transcriptomics reveals glycolysis heterogeneity and NEK6-mediated progression in colorectal cancer. Frontiers in immunology 0 42131349
2026 NEK6 Knockout Causes Defects in Mitochondrial Morphology and Respiration. Cells 0 42193938
2025 Design and synthesis of pyridopyrimidines targeting NEK6 kinase. Archives of biochemistry and biophysics 0 40090442

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