Affinage

NUAK1

NUAK family SNF1-like kinase 1 · UniProt O60285

Length
661 aa
Mass
74.3 kDa
Annotated
2026-06-10
95 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NUAK1 (ARK5) is an AMPK-related serine/threonine kinase that couples upstream growth-factor and energy-stress signaling to control of cell survival, metabolism, the cytoskeleton, mitochondrial behavior, and gene expression, with prominent roles in both neuronal development and tumor biology (PMID:23791179, PMID:29500295). It is activated by T-loop phosphorylation at Thr211 by LKB1 and by NDR2 during IGF-1 signaling, with AKT phosphorylating a separate regulatory-domain site (Ser600); in LKB1-null tumor cells a calcium/PKCα route maintains NUAK1 activity to engage the AMPK-TORC1 metabolic checkpoint (PMID:21317932, PMID:16488889, PMID:29106388). A recurring effector mechanism is NUAK1 inhibition of the PP1β-MYPT1 phosphatase, which it exploits to activate PLK1 and PLK4 in centrosome duplication and to promote GSK3β-dependent nuclear import of the antioxidant regulator NRF2, linking the kinase to genomic stability and redox control (PMID:24785407, PMID:29500295, PMID:36975767). Through direct substrate phosphorylation NUAK1 acts on diverse targets: tau at Ser356 to stabilize it and drive tauopathy (PMID:27720485), caspase-6 at Ser257 to block apoptosis (PMID:15273717), LATS1 at Ser464 to promote senescence (PMID:19927127), IRS1 at Ser1097 to suppress insulin signaling in muscle (PMID:22418434), NADK at Ser64 to mitigate ROS (PMID:39159134), and the RNA-processing factors PNUTS and hnRNP A1 to control splicing and stress-dependent relocalization (PMID:32006464, PMID:35963429). In neurons the LKB1-NUAK1 pathway controls cortical axon branching by immobilizing mitochondria at presynaptic sites and by regulating mitochondrial metabolism via the microprotein BRAWNIN (PMID:23791179, PMID:38514619). In cancer NUAK1 promotes invasion, fibronectin-dependent spheroid integrity, and chemoresistance, and is a TGF-β-inducible profibrotic kinase that sustains YAP and TGF-β/SMAD signaling in a positive feedback loop driving organ fibrosis (PMID:15060171, PMID:35320001, PMID:32429240). NUAK1 itself is regulated by a CDK→PLK→SCFβTrCP degradation cascade and by USP9X-mediated deubiquitylation, and shuttles between nucleus and cytoplasm via importin-β/IPO7/IPO9-dependent nuclear import that is blocked by oxidative stress (PMID:24785407, PMID:31090959, PMID:40310323).

Mechanistic history

Synthesis pass · year-by-year structured walk · 36 steps
  1. 2003 Medium

    Established NUAK1/ARK5 as an anti-apoptotic kinase, defining its first cellular role in protecting cells from death-receptor and metabolic stress.

    Evidence ARK5 overexpression in HepG2 cells with Bid/FLIP/caspase-8 immunoblotting and cell death assays under multiple stimuli

    PMID:13679856

    Open questions at the time
    • Direct substrate in the caspase-8 axis not identified here
    • Overexpression-only; loss-of-function not tested
  2. 2004 High

    Identified the first direct NUAK1 substrate mediating apoptosis resistance, showing it phosphorylates procaspase-6 at Ser257 to block its activation.

    Evidence Antisense knockdown, caspase-6 S257A mutagenesis and in vitro kinase assay in colorectal cancer cells

    PMID:15273717

    Open questions at the time
    • In vivo relevance of the phospho-site not established
    • Did not address kinase activation requirements
  3. 2004 Medium

    Placed NUAK1 downstream of Akt as a driver of tumor invasion via MMP induction, linking the kinase to metastatic phenotypes.

    Evidence Matrigel invasion, MMP activity assays, rapamycin treatment and nude mouse tumor model

    PMID:15060171

    Open questions at the time
    • Direct kinase substrate driving MMP expression unknown
    • Single lab, overexpression-based
  4. 2005 Medium

    Defined transcriptional control of NUAK1, showing Large-MAF factors drive its expression to mediate IGF-1-induced myeloma invasion.

    Evidence Promoter MARE analysis, luciferase reporter mutagenesis, ChIP and invasion assays

    PMID:16044163

    Open questions at the time
    • MAF regulation not shown in other tissue contexts
  5. 2006 High

    Resolved how NUAK1 is activated, identifying NDR2 as the Thr211 T-loop kinase during IGF-1 signaling and AKT as a separate Ser600 activator.

    Evidence In vitro kinase assays with NDR2/ARK5, Thr211 mutagenesis, co-IP and IGF-1 stimulation

    PMID:16488889

    Open questions at the time
    • Relative contributions of NDR2 versus LKB1 to T211 phosphorylation not delineated
  6. 2009 Medium

    Connected NUAK1 to senescence and genome instability, showing it phosphorylates and destabilizes LATS1 at Ser464.

    Evidence Loss-of-function fibroblast screen, shRNA/overexpression, LATS1 phospho-assay and dominant-negative epistasis

    PMID:19927127

    Open questions at the time
    • Mechanism linking LATS1 loss to aneuploidy not fully resolved
    • Single lab
  7. 2011 Medium

    Linked LKB1-NUAK1 to p53-dependent cell-cycle arrest, showing NUAK1 binds and phosphorylates p53 and occupies the p21 promoter.

    Evidence Co-IP, in vitro kinase assay, ChIP on p21/WAF1 promoter and cell-cycle analysis with kinase-dead mutants

    PMID:21317932

    Open questions at the time
    • p53 phospho-site not mapped
    • Direct DNA binding by NUAK1 vs. recruitment unclear
  8. 2012 High

    Established NUAK1 as a negative regulator of insulin signaling in muscle via IRS1 Ser1097 phosphorylation.

    Evidence Muscle-specific knockout mice, quantitative phosphoproteomics of soleus, insulin signaling and glucose tolerance assays

    PMID:22418434

    Open questions at the time
    • Direct vs. indirect IRS1 phosphorylation not separated
    • Whole-body metabolic consequences limited
  9. 2012 Medium

    Revealed a developmental cytoskeletal role, showing NUAK1/NUAK2 redundantly drive apical constriction during neural plate hinge-point formation.

    Evidence NUAK1/NUAK2 double-mutant mice with immunostaining for phospho-MLC2, F-actin, cortactin and acetylated tubulin

    PMID:22689267

    Open questions at the time
    • Direct cytoskeletal substrate not identified
    • Redundancy obscures NUAK1-specific function
  10. 2013 High

    Defined the canonical neuronal function, showing the LKB1-NUAK1 pathway promotes axon branching by immobilizing presynaptic mitochondria.

    Evidence Conditional KO, in vivo KD/OE, live mitochondrial imaging and Syntaphilin genetic epistasis

    PMID:23791179

    Open questions at the time
    • Direct substrate controlling mitochondrial arrest not identified at this stage
  11. 2013 Medium

    Identified upstream miRNA control, placing NUAK1 in a MITF/miR-211 axis that governs melanoma adhesion.

    Evidence miR-211 gain/loss-of-function, NUAK1 3'UTR luciferase reporter and adhesion assays

    PMID:23934065

    Open questions at the time
    • Downstream NUAK1 substrate in adhesion not defined
  12. 2014 High

    Solved NUAK1 protein turnover and a key effector node, defining a CDK→PLK→SCFβTrCP degradation cascade and NUAK1 activation of PLK1 through PP1β-MYPT1 inhibition.

    Evidence Co-IP, phospho-site mutagenesis (Ser445/476/480), ubiquitylation assays, NUAK1 inhibitors and cell-cycle synchronization

    PMID:24785407

    Open questions at the time
    • Physiological triggers of CDK-driven degradation not mapped
  13. 2017 Medium

    Identified an LKB1-independent activation route, showing calcium/PKCα sustains NUAK1 activity in LKB1-null tumors to support AMPK-TORC1 and MYC cell survival.

    Evidence Calcium manipulation, PKCα inhibition/knockdown, NUAK1 activity and MYC-dependent viability assays

    PMID:29106388

    Open questions at the time
    • PKCα phospho-site on NUAK1 not mapped
  14. 2018 High

    Connected NUAK1 to redox-driven oncogenesis, showing it promotes NRF2 nuclear import via PP1β/AKT/GSK3β and is required for colorectal tumor maintenance.

    Evidence Genetic NUAK1 deletion in autochthonous colorectal cancer model, PP1β/GSK3β assays, NRF2 fractionation and pharmacological inhibition

    PMID:29500295

    Open questions at the time
    • Direct NUAK1 substrate within the NRF2 import machinery not resolved beyond PP1β
  15. 2019 Medium

    Established the basis of NUAK1 nucleocytoplasmic shuttling, identifying a bipartite NLS and importin-β/IPO7/IPO9-dependent import inhibited by oxidative stress.

    Evidence NLS prediction/deletion mutants, importin knockdown, importazole, MS of NUAK1-importin interactions and immunofluorescence

    PMID:31090959

    Open questions at the time
    • Mechanism by which oxidative stress blocks import not defined
  16. 2020 High

    Defined a nuclear transcriptional-coupling function, showing NUAK1 phosphorylates the PP1 subunit PNUTS to sustain spliceosome activity and productive RNAPII elongation in MYC-driven cells.

    Evidence Nuclear fractionation, proximity proteomics, in vitro PNUTS phosphorylation, spliceosome and nascent RNA assays, RNAPII ChIP-seq and inhibitors

    PMID:32006464

    Open questions at the time
    • PNUTS phospho-sites not mapped
    • Generality beyond MYC-transformed cells untested
  17. 2020 Medium

    Extended NUAK1 into mTORC2/Akt signaling, showing it directly phosphorylates Akt Ser473 and regulates mTOR lysosome positioning.

    Evidence Co-IP with mTORC2 components, in vitro Akt phosphorylation, lysosome positioning and endosome fractionation

    PMID:38135881

    Open questions at the time
    • Reconciliation with NUAK1 being downstream of Akt elsewhere unresolved
  18. 2020 Medium

    Began dissecting compartment-specific metabolic roles, linking cytosolic NUAK1 to respiration/glycolysis and mitochondrial morphology.

    Evidence Subcellular fractionation, Seahorse respiration, ATP measurement and mitochondrial morphology imaging

    PMID:32754444

    Open questions at the time
    • Molecular substrate controlling mitochondrial morphology not identified
  19. 2020 Medium

    Showed NUAK1 maintains fibronectin-dependent ovarian cancer spheroid integrity downstream of LKB1.

    Evidence CRISPR NUAK1 KO, LKB1-NUAK1 phospho-assays, transcriptomics, fibronectin rescue and xenograft metastasis

    PMID:32429240

    Open questions at the time
    • Mechanism linking NUAK1 kinase activity to FN1 transcription unknown
  20. 2020 Medium

    Connected NUAK1 inhibition to immunogenic cell death via NRF2/ROS, revealing a mevalonate-pathway negative-feedback brake.

    Evidence Kinome-wide CRISPR screen, NRF2 reporters, ROS and ICD markers, simvastatin and cholesterol rescue

    PMID:39824180

    Open questions at the time
    • Direct NUAK1 substrate in this axis beyond NRF2 regulation not defined
  21. 2016 High

    Identified NUAK1 as a tau-stabilizing kinase, defining direct Ser356 phosphorylation as a therapeutic node in tauopathy.

    Evidence Cell and Drosophila genetic screens, in vitro/in vivo phospho-assays and mouse tauopathy haploinsufficiency

    PMID:27720485

    Open questions at the time
    • Mechanism by which Ser356 phosphorylation stabilizes tau not fully resolved
  22. 2022 High

    Established NUAK1 as a core profibrotic kinase, defining a TGF-β→NUAK1→YAP/SMAD positive feedback loop driving fibrosis across organs.

    Evidence Fibroblast-specific conditional KO, pharmacological inhibition and kidney/lung/liver fibrosis models

    PMID:35320001

    Open questions at the time
    • Direct NUAK1 substrate in the YAP/SMAD circuit not identified
  23. 2022 High

    Defined NUAK1 control of hnRNP A1 stress relocalization through phosphorylation in the F-peptide/M9 region.

    Evidence Co-IP, in vitro kinase assay, M9-motif mutagenesis, fractionation and caspase activation assays

    PMID:35963429

    Open questions at the time
    • Functional consequences for specific mRNA targets not mapped
  24. 2022 Medium

    Identified USP9X as the deubiquitinase that stabilizes and activates NUAK1 to drive myofibroblast transformation.

    Evidence Myofibroblast-specific USP9X KO, inhibition, co-IP and deubiquitination assays with Rho-kinase readouts

    PMID:40310323

    Open questions at the time
    • Ubiquitin-chain specificity and site on NUAK1 not defined
  25. 2022 Medium

    Showed NUAK1 sustains TGF-β signaling in hepatic stellate cells by suppressing Smurf2-mediated TβRI/Smad4 degradation.

    Evidence HTH-01-015 inhibition, siRNA in HSC/hepatocytes, receptor stability assays and CCl4 liver fibrosis model

    PMID:36361872

    Open questions at the time
    • Direct NUAK1 substrate controlling Smurf2 not identified
  26. 2023 Medium

    Extended the PP1β effector axis to centrosome biology, showing NUAK1 governs PLK4-dependent centrosome duplication and genomic stability.

    Evidence NUAK1 inhibition/depletion in PDAC and fibroblasts, centrosome counting and MYPT1/PP1β/GSK3β/PLK4 pathway analysis

    PMID:36975767

    Open questions at the time
    • Whether NUAK1 loss causes amplification vs. failed duplication context-dependent
  27. 2023 Medium

    Linked NUAK1 to ESCC metastasis through JNK/c-Jun-driven Slug transcription.

    Evidence Co-IP, Slug promoter luciferase, JNK/c-Jun inhibition and pulmonary metastasis model

    PMID:37919754

    Open questions at the time
    • Direct kinase event upstream of JNK not defined
  28. 2024 High

    Refined the neuronal mechanism, showing NUAK1 controls axon branching through mitochondrial metabolism and the microprotein BRAWNIN, not just mitochondrial positioning.

    Evidence In vivo/in vitro NUAK1 KO neurons, mitochondrial and ATP assays, and BRAWNIN-based rescue

    PMID:38514619

    Open questions at the time
    • How NUAK1 regulates BRAWNIN molecularly not resolved
  29. 2024 High

    Defined a redox-protective oncogenic substrate, showing NUAK1 phosphorylates NADK Ser64 to mitigate ROS and confer osimertinib resistance.

    Evidence Co-IP, in vitro kinase assay, NADK S64 mutagenesis, ROS measurement and xenograft

    PMID:39159134

    Open questions at the time
    • Quantitative contribution of NADK phosphorylation to NADP(H) pools not measured
  30. 2024 Medium

    Linked NUAK1 to gastric cancer chemoresistance via a STAT5/GLI1 signaling axis.

    Evidence Depletion/inhibition, PDX and transgenic models, STAT5 activity and GLI1 stability assays with co-IP

    PMID:38996065

    Open questions at the time
    • Direct NUAK1 phospho-target in the STAT5/GLI1 axis unknown
  31. 2024 Medium

    Showed NUAK1 promotes mitochondrial fission to support myeloma bioenergetics.

    Evidence Biallelic ARK5 KO, mitochondrial morphology imaging, fusion/fission protein blots and metabolic assays

    PMID:38282096

    Open questions at the time
    • Whether NUAK1 directly phosphorylates DRP1 not established
  32. 2024 Medium

    Linked NUAK1 to MASH liver injury via caspase-6 activation and TAK1-RIPK1 regulation of pyroptosis.

    Evidence NUAK1 inhibition in MASH models, caspase-6 disruption and TAK1-RIPK1 co-IP/degradation assays

    PMID:38967580

    Open questions at the time
    • Reconciliation with earlier caspase-6 inhibition finding context-dependent
  33. 2024 Medium

    Provided the first NUAK1 crystal structure and exploited Glu139 to develop subnanomolar selective inhibitors, enabling cleaner mechanistic dissection.

    Evidence X-ray crystallography of a NUAK1 chimera and inhibitor co-crystal structures with SAR

    PMID:39588908

    Open questions at the time
    • Full-length, substrate-bound NUAK1 structure not obtained
  34. 2024 Medium

    Identified PSD3 Ser476 as a direct NUAK1 substrate controlling ARF6 activity and dendritic spine maturation.

    Evidence ATP-analog-sensitive chemical genetics, direct phospho-assay, S476A mutant, ARF6/PI(4,5)P2 imaging and spine analysis (preprint)

    PMID:42079242

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • In vivo relevance to circuit function untested
  35. 2025 Medium

    Defined a NUAK1-SON pathway controlling alternative splicing in developing cortical neurons.

    Evidence NUAK1 KO neurons, SON phosphorylation assays, RNA-seq splicing analysis and SON knockdown phenocopy (preprint)

    PMID:bio_10.1101_2025.10.10.681550

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • SON phospho-sites not mapped
  36. 2025 Medium

    Linked NUAK1 to immune evasion, showing it drives PD-L1 transcription via GSK3β/β-catenin in HCC.

    Evidence Gain/loss-of-function, p-GSK3β/β-catenin blots, nuclear fractionation and β-catenin knockdown rescue

    PMID:39901136

    Open questions at the time
    • Direct NUAK1 substrate upstream of GSK3β not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether NUAK1's many context-specific outputs converge on a small set of direct substrates (e.g. the PP1β-MYPT1 node) or reflect a broad, tissue-tuned substrate repertoire remains unresolved.
  • No unified substrate map across tissues
  • Direct vs. PP1β-indirect effects not systematically separated
  • Compartment-specific (nuclear vs. cytoplasmic) substrate sets incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016740 transferase activity 5 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1430728 Metabolism 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
HNRNP A1LKB1NADKNDR2P53PNUTSPP1Β-MYPT1USP9X

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 LKB1 activates NUAK1, and the LKB1-NUAK1 kinase pathway regulates cortical axon branching by promoting mitochondria immobilization at nascent presynaptic sites; conditional deletion or knockdown of either kinase drastically reduced axon branching in vivo, while overexpression increased it. Conditional knockout, in vivo knockdown/overexpression, live imaging of mitochondrial transport, genetic epistasis with Syntaphilin Cell High 23791179
2024 NUAK1 deficiency impairs mitochondrial metabolism and axonal ATP concentration; upregulation of mitochondrial function rescues axonal branching in NUAK1-null neurons. NUAK1 regulates axon branching through the mitochondria-targeted microprotein BRAWNIN, exerting a dual function by controlling both mitochondrial distribution and metabolic activity. In vitro and in vivo neuronal cultures with NUAK1 knockout, mitochondrial function assays, ATP measurements, rescue experiments with mitochondrial activators, identification of BRAWNIN as downstream effector Nature communications High 38514619
2016 NUAK1 stabilizes tau by direct phosphorylation specifically at Ser356; inhibition of NUAK1 reduces steady-state tau levels and suppresses neurodegeneration in tau-expressing Drosophila, and NUAK1 haploinsufficiency rescues tauopathy phenotypes in mice. Parallel cell-based and Drosophila genetic screens, in vitro/in vivo phosphorylation assays, genetic loss-of-function in mouse tauopathy model Neuron High 27720485
2003 ARK5 (NUAK1) suppresses cell death by glucose starvation and death receptor stimulation (TRAIL, TNF-α) by inhibiting caspase 8 activation; ARK5 overexpression delayed Bid cleavage, FLIP degradation, and caspase 8 activation. This protective effect was not observed for UV irradiation, camptothecin, or doxorubicin. ARK5 overexpression in HepG2 cells, Western blotting for Bid cleavage/FLIP degradation/caspase 8 activation, cell death assays under multiple stimuli Oncogene Medium 13679856
2004 ARK5 (NUAK1) phosphorylates and inhibits procaspase-6 at Ser257, preventing its activation and subsequent FLIP degradation, thereby mediating resistance to FasL/Fas-induced cell death in colorectal cancer cells; in vitro kinase assay showed ARK5 phosphorylates wild-type but not caspase-6/S257A mutant. ARK5 antisense RNA knockdown, caspase-6 mutagenesis (Ser257Ala), in vitro kinase assay, Western blotting, cell death assays Oncogene High 15273717
2004 ARK5 (NUAK1) promotes tumor invasion downstream of Akt signaling; ARK5 expression induces activation of MMP-2, MMP-9, and new expression of MT1-MMP via rapamycin-sensitive signaling, and ARK5-overexpressing tumor cells show invasion and metastasis in nude mice. Matrigel invasion assay, MMP activity assays, rapamycin treatment, nude mouse tumor model Molecular and cellular biology Medium 15060171
2009 NUAK1 promotes cellular senescence and aneuploidization by phosphorylating LATS1 at Ser464, destabilizing LATS1; ectopic NUAK1 expression triggers premature senescence with gross aneuploidies, while NUAK1 depletion extends replicative lifespan and increases LATS1 levels. Loss-of-function screen in diploid fibroblasts, shRNA depletion, ectopic overexpression, Western blotting, LATS1 phosphorylation assay, dominant-negative LATS1 The EMBO journal Medium 19927127
2011 NUAK1 directly interacts with and phosphorylates p53 in vitro and in vivo; this requires NUAK1 kinase activity and phosphorylation at Thr211 by LKB1. LKB1/NUAK1 activation leads to G1/S cell cycle arrest by inducing p21/WAF1 expression; NUAK1 binds p53-responsive elements of the p21/WAF1 promoter in the nucleus. Co-immunoprecipitation, in vitro kinase assay, ChIP on p21/WAF1 promoter, cell cycle analysis, kinase-dead mutants Oncogene Medium 21317932
2006 NDR2 is an upstream kinase of ARK5 (NUAK1) that directly phosphorylates the conserved Thr211 on the active T-loop of ARK5 during IGF-1 signaling, enabling full ARK5 activation; AKT phosphorylates ARK5 at Ser600 in the regulatory domain as a separate activating event. In vitro kinase assay with NDR2 and ARK5, phosphorylation site mutagenesis (Thr211), co-immunoprecipitation, IGF-1 stimulation experiments The Journal of biological chemistry High 16488889
2014 NUAK1 expression is controlled by CDK-PLK-SCFβTrCP E3 ubiquitin ligase complex: CDK phosphorylates NUAK1 at Ser445, triggering PLK binding, which phosphorylates NUAK1 at Ser476 and Ser480, inducing βTrCP binding, ubiquitylation and degradation. NUAK1 also activates PLK1 via inhibition of the PP1β-MYPT1 phosphatase that dephosphorylates PLK1 Thr210. Co-immunoprecipitation, phosphorylation site mutagenesis (Ser445, Ser476, Ser480), ubiquitylation assays, NUAK1 inhibitors (WZ4003, HTH-01-015), cell cycle synchronization, rescue with phospho-mutant NUAK1 The Biochemical journal High 24785407
2005 ARK5 (NUAK1) is a transcriptional target of the Large-MAF family (c-MAF, MAFB) via MAF-recognition element (MARE) sequences in its promoter; ARK5 mediates IGF-1-induced cell invasion in multiple myeloma downstream of MAF transcription factors. Gene expression profiling, promoter sequence analysis with MARE identification, luciferase reporter with MARE deletion/mutation, chromatin immunoprecipitation (ChIP), ARK5 overexpression in non-expressing cell lines, invasion assays Oncogene Medium 16044163
2018 NUAK1 is activated by oxidative stress and facilitates nuclear import of the antioxidant master regulator NRF2: activated NUAK1 inhibits PP1β, which cooperates with AKT activation to suppress GSK3β-dependent phosphorylation that normally prevents NRF2 nuclear import; deletion of NUAK1 suppresses colorectal tumor formation and induces regression of preexisting autochthonous tumors. Genetic NUAK1 deletion in autochthonous mouse colorectal cancer model, PP1β inhibition assays, GSK3β phosphorylation analysis, NRF2 nuclear fractionation, pharmacological NUAK1 inhibition Cancer discovery High 29500295
2022 NUAK1 is a TGF-β-inducible profibrotic kinase; TGF-β rapidly induces NUAK1 in fibroblasts, which in turn promotes profibrotic YAP and TGF-β/SMAD signaling; activated YAP/TAZ further induces NUAK1 expression, creating a positive feedback loop. Fibroblast-specific NUAK1 loss or pharmacologic NUAK1 inhibition attenuates fibrosis in kidney, lung, and liver mouse models. Fibroblast-specific conditional NUAK1 knockout mice, pharmacological NUAK1 inhibition, multiple organ fibrosis mouse models, YAP/SMAD signaling assays Science translational medicine High 35320001
2020 NUAK1 is a predominantly nuclear protein that associates with nuclear PP1 interactors including PNUTS (a nuclear regulatory subunit of PP1) and phosphorylates PNUTS; both NUAK1 and PNUTS associate with the splicing machinery. NUAK1 inhibition abolishes chromatin association of PNUTS, reduces spliceosome activity, suppresses nascent RNA synthesis, and in MYC-transformed cells traps non-productive RNAPII at the pause site and first exon-intron boundary. Nuclear fractionation, Co-IP/proximity proteomics, in vitro phosphorylation of PNUTS, spliceosome activity assays, nascent RNA synthesis measurement, RNAPII ChIP-seq, NUAK1 inhibitors Molecular cell High 32006464
2017 In tumor cells lacking LKB1, NUAK1 activity is maintained by an alternative pathway: calcium-dependent activation of PKCα phosphorylates and activates NUAK1, supporting AMPK-TORC1 metabolic checkpoint engagement and protecting MYC-overexpressing tumor cells from cell death. Pharmacological calcium manipulation, PKCα inhibition/knockdown, NUAK1 activity assays, AMPK-TORC1 signaling readouts, MYC-dependent cell viability assays Oncogene Medium 29106388
2012 NUAK1-deficient muscle shows decreased phosphorylation of IRS1 at Ser1097, leading to enhanced insulin signaling (increased phosphorylation of IRS1 Tyr608, AKT Thr308, TBC1D4 Thr649), suggesting NUAK1 negatively regulates insulin signaling in oxidative muscle through IRS1 Ser1097 phosphorylation. Muscle-specific NUAK1 knockout mice, quantitative phosphoproteome analysis of soleus muscle, insulin signaling assays, glucose tolerance tests The Journal of biological chemistry High 22418434
2012 NUAK1 and NUAK2 complementarily function in apical constriction and apico-basal elongation during dorsolateral hinge point formation in cephalic neural plate; NUAK1/NUAK2 double mutants show reduced apical concentration of phosphorylated myosin light chain 2, F-actin, and cortactin, and impaired development of acetylated α-tubulin-positive microtubules. NUAK1/NUAK2 double mutant mouse analysis, immunostaining for phospho-MLC2, F-actin, cortactin, acetylated α-tubulin Developmental dynamics Medium 22689267
2019 NUAK1 contains a conserved bipartite nuclear localization signal (NLS) at its N-terminal domain and is actively imported into the nucleus by importin-β members KPNB1 (importin-β1), IPO7 (importin-7), and IPO9 (importin-9); oxidative stress induces NUAK1 cytoplasmic accumulation by inhibiting this nuclear transport. Bioinformatics NLS prediction, subcellular fractionation, NLS deletion mutants, importin knockdown (IPO7, IPO9 siRNA), importazole treatment, mass spectrometry identification of NUAK1-importin interactions, immunofluorescence Journal of cellular biochemistry Medium 31090959
2020 Cytosolic NUAK1 increases ATP levels via increased mitochondrial respiration and maintains glycolytic capacity under mitochondrial inhibition; NUAK1 inhibition leads to 'donut-like' mitochondrial morphology changes indicating NUAK1-dependent mitochondrial morphology regulation. Nuclear NUAK1 appears involved in the metabolic switch to glycolysis. Subcellular fractionation, mitochondrial respiration assays (Seahorse), ATP measurement, NUAK1 inhibition, mitochondrial morphology imaging Frontiers in oncology Medium 32754444
2022 ARK5 (NUAK1) directly interacts with and phosphorylates hnRNP A1 on serine residues within the F-peptide region; the M9 motif of hnRNP A1 is essential for this interaction and phosphorylation. ARK5-mediated phosphorylation of hnRNP A1 controls its cytoplasmic relocalization during hypertonic stress; ARK5 silencing increases Bcl-xL expression and delays caspase activation. Immunoprecipitation, in vitro kinase assay, hnRNP A1 domain mutagenesis (M9 motif deletion), subcellular fractionation, siRNA knockdown, caspase activation assays The Journal of biological chemistry High 35963429
2020 NUAK1 coordinates growth factor-dependent mTORC2 and Akt activation by two mechanisms: (1) interacting with mTORC2 components and regulating mTOR lysosome positioning; (2) directly phosphorylating Akt at Ser473. NUAK1 selectively promotes Akt-dependent phosphorylation of FOXO1/3a but not TSC2, and is associated with early endosomes. Co-immunoprecipitation with mTORC2 components, in vitro Akt phosphorylation assays, lysosome positioning analysis, subcellular fractionation (early endosome), NUAK1 inhibitors, specific substrate phosphorylation analysis Cell & bioscience Medium 38135881
2023 NUAK1 governs centrosome duplication in pancreatic cancer via MYPT1/PP1β and GSK3β-dependent regulation of PLK4; loss of NUAK1 triggers genomic instability through inaccurate centrosome duplication, an effect conserved in primary fibroblasts. NUAK1 inhibition and depletion in PDAC cells, centrosome counting, genomic instability assays, MYPT1/PP1β and GSK3β-PLK4 pathway analysis Molecular oncology Medium 36975767
2024 NUAK1 directly phosphorylates NADK (nicotinamide adenine dinucleotide kinase) at Ser64, which mitigates osimertinib-induced ROS accumulation and confers osimertinib resistance in NSCLC; NUAK1-NADK interaction was confirmed by co-immunoprecipitation and in vitro kinase assay. Co-immunoprecipitation, in vitro kinase assay, phosphorylation site mutagenesis (NADK Ser64), ROS measurement, genetic/pharmacological NUAK1 blockade, in vivo xenograft Cancer research High 39159134
2024 NUAK1 activates STAT5-mediated transcription and stabilizes GLI1 protein in gastric cancer, promoting cancer cell expansion and chemotherapy resistance through the NUAK1/STAT5/GLI1 signaling axis. NUAK1 depletion/inhibition, patient-derived xenograft and transgenic mouse models, STAT5 transcriptional activity assays, GLI1 protein stability assays, co-immunoprecipitation Cell reports Medium 38996065
2020 NUAK1 loss in ovarian cancer spheroids dramatically reduces FN1 gene expression (fibronectin), which is required for spheroid integrity; LKB1 maintains NUAK1 phosphorylation and promotes its stabilization; NUAK1KO spheroids show reduced integrity and increased cell death, rescued by co-incubation with soluble fibronectin. CRISPR NUAK1 KO in EOC cells, LKB1-NUAK1 phosphorylation assays, transcriptome analysis, fibronectin rescue experiments, xenograft metastasis model Cancers Medium 32429240
2020 NUAK1 inhibition increases ROS via downregulation of NRF2-mediated antioxidant gene expression, triggering immunogenic cell death (ICD); XBP1s downstream of ICD-induced ER stress activates the mevalonate/cholesterol pathway as a negative feedback mechanism that dampens ROS and ICD. Kinome-wide CRISPR-Cas9 screen, NRF2 reporter assays, ROS measurement, ICD markers, HMGCR inhibition with simvastatin, cholesterol supplementation experiments Cell reports. Medicine Medium 39824180
2023 NUAK1 promotes ESCC metastasis by enhancing Slug transcription through activation of the JNK/c-Jun pathway; silencing Slug completely abolishes migration and invasion of NUAK1-overexpressing ESCC cells; NUAK1 and Slug interact as shown by co-immunoprecipitation. Co-immunoprecipitation, dual-luciferase reporter assay for Slug promoter, JNK/c-Jun inhibition, NUAK1 overexpression/knockdown, in vivo pulmonary metastasis model Cancer cell international Medium 37919754
2022 USP9X deubiquitinates and activates ARK5 (NUAK1), promoting TGF-β1-induced myofibroblast transformation via the Rho kinase pathway; USP9X-ARK5 interaction demonstrated by binding and deubiquitination assays. Myofibroblast-specific USP9X knockout, pharmacological USP9X inhibition, co-immunoprecipitation, deubiquitination assay, ARK5 activation assays, Rho kinase pathway analysis JACC. Basic to translational science Medium 40310323
2024 ARK5 (NUAK1) enhances mitochondrial fission in multiple myeloma; ARK5 knockout leads to enhanced mitochondrial fusion (increased MFN1, MFN2, OPA1), reduced phospho-DRP1 (Ser616), lower ATP levels, higher lactate and ROS, showing ARK5 promotes mitochondrial fission for bioenergetic support. Biallelic ARK5 knockout in MM cell lines, mitochondrial morphology imaging, Western blotting for fusion/fission proteins, ATP measurement, ROS and lactate assays Cell death discovery Medium 38282096
2022 In hepatic stellate cells, ARK5 (NUAK1) prevents degradation of TGF-β type I receptor (TβRI) and Smad4 by inhibiting Smurf2 expression, maintaining continuous TGF-β signaling; in hepatocytes, ARK5 induces EMT and promotes secretion of inflammatory factors that further activate HSCs. ARK5 inhibition with HTH-01-015, siRNA knockdown in HSC and hepatocyte cell lines, TβRI/Smad4 stability assays, Smurf2 expression analysis, CCl4-induced liver fibrosis mouse model International journal of molecular sciences Medium 36361872
2024 NUAK1 promotes MASH-related liver injury by facilitating Caspase 6 activation and triggering pyroptosis; NUAK1/Caspase 6 axis inhibition accelerates interaction between TAK1 and RIPK1, leading to RIPK1 degradation and reduced inflammation. NUAK1 inhibition in MASH mouse models, Caspase 6 disruption, TAK1-RIPK1 co-immunoprecipitation, RIPK1 degradation assays Hepatology communications Medium 38967580
2025 NUAK1 promotes PD-L1 transcriptional expression in hepatocellular carcinoma by activating GSK3β Ser9 phosphorylation, leading to β-catenin nuclear accumulation and transcriptional activation of PD-L1; knockdown of β-catenin reverses NUAK1-mediated PD-L1 upregulation. NUAK1 gain/loss-of-function, Western blotting for p-GSK3β/β-catenin, nuclear fractionation, β-catenin knockdown rescue, immunohistochemistry on patient samples Molecular medicine (Cambridge, Mass.) Medium 39901136
2020 Yeast Tda1, the ortholog of human NUAK1, is a direct kinase for histone H3 threonine 11 (H3pT11) upon low glucose stress; yeast AMPK directly phosphorylates Tda1 to govern its activity, while CK2 regulates Tda1 nuclear localization, thus linking glucose stress to chromatin regulation. In vitro kinase assay with Tda1 and histone H3, phosphorylation site identification (H3pT11), genetic epistasis in yeast (AMPK and CK2 mutants), nuclear localization analysis eLife Medium 33372657
2013 miR-211 targets NUAK1 directly, reducing NUAK1 expression and promoting melanoma cell adhesion; inhibition of miR-211 increases NUAK1 expression and decreases melanoma adhesion, while upregulation of miR-211 restores adhesion through NUAK1 repression. This defines the MITF/miR-211/NUAK1 axis as an inhibitor of the melanoma invasive program. miR-211 gain/loss-of-function, luciferase reporter assay for NUAK1 3'UTR targeting, adhesion assays, NUAK1 knockdown The Journal of investigative dermatology Medium 23934065
2024 NUAK1 phosphorylates PSD3 (Pleckstrin Homology and Sec7-domain containing protein 3) at Ser476; phospho-deficient PSD3 leads to aberrant ARF6 activation and PI(4,5)P2 accumulation in intracellular vesicles, and in neurons leads to enhanced spine maturation in an ARF6-dependent fashion. ATP-analog sensitive NUAK1 chemical genetics screen, direct phosphorylation assay of PSD3, phospho-deficient mutant PSD3 (S476A), ARF6 activation assays, PI(4,5)P2 imaging, dendritic spine analysis in neurons bioRxivpreprint Medium 42079242
2025 NUAK1 regulates alternative splicing in developing cortical neurons through phosphorylation of the splicing co-factor SON, controlling conserved splicing events in genes crucial for neurodevelopment; this NUAK1-SON pathway is required for proper neuronal development. NUAK1 knockout in cortical neurons, phosphorylation assays for SON, alternative splicing analysis (RNA-seq), SON knockdown phenocopy experiments bioRxivpreprint Medium bio_10.1101_2025.10.10.681550
2024 NUAK1 is present in human erythrocytes, undergoes increased phosphorylation in P. falciparum-infected cells, and is required for parasite invasion; pharmacological NUAK1 inhibition reduces MYPT1 phosphorylation in erythroid cells and inhibits parasite growth; NUAK1 overexpression partially rescues invasion phenotypes caused by inhibitors. NUAK1 inhibitors (HTH-01-015, WZ4003) with chemoproteomic selectivity profiling, MYPT1 phosphorylation assays, NUAK1 overexpression rescue, parasite invasion assays bioRxivpreprint Medium 41278793
2024 NUAK1 crystal structure obtained using a chimeric protein; structure-guided drug design exploiting the unique Glu139 residue of NUAK1 enabled development of highly selective inhibitors with subnanomolar potency. X-ray crystallography of NUAK1 chimeric protein, structure-activity relationship, co-crystal structures of inhibitor-NUAK1 complexes Journal of medicinal chemistry Medium 39588908

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Terminal axon branching is regulated by the LKB1-NUAK1 kinase pathway via presynaptic mitochondrial capture. Cell 287 23791179
2021 Suppressing the KIF20A/NUAK1/Nrf2/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin. Aging 135 33819186
2016 Reduction of Nuak1 Decreases Tau and Reverses Phenotypes in a Tauopathy Mouse Model. Neuron 125 27720485
2004 ARK5 is a tumor invasion-associated factor downstream of Akt signaling. Molecular and cellular biology 112 15060171
2013 Transcription factor/microRNA axis blocks melanoma invasion program by miR-211 targeting NUAK1. The Journal of investigative dermatology 98 23934065
2014 MiR-204 inhibits human NSCLC metastasis through suppression of NUAK1. British journal of cancer 96 25412236
2009 Regulation of ploidy and senescence by the AMPK-related kinase NUAK1. The EMBO journal 93 19927127
2022 NUAK1 promotes organ fibrosis via YAP and TGF-β/SMAD signaling. Science translational medicine 89 35320001
2018 Colorectal Tumors Require NUAK1 for Protection from Oxidative Stress. Cancer discovery 81 29500295
2003 ARK5 suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but not by chemotherapeutic agents or UV irradiation. Oncogene 77 13679856
2004 Regulation of caspase-6 and FLIP by the AMPK family member ARK5. Oncogene 76 15273717
2011 A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation. Oncogene 68 21317932
2018 LncRNA SNHG1 functions as a ceRNA to antagonize the effect of miR-145a-5p on the down-regulation of NUAK1 in nasopharyngeal carcinoma cell. Journal of cellular and molecular medicine 67 29575772
2005 ARK5 is transcriptionally regulated by the Large-MAF family and mediates IGF-1-induced cell invasion in multiple myeloma: ARK5 as a new molecular determinant of malignant multiple myeloma. Oncogene 60 16044163
2012 ARK5 promotes glioma cell invasion, and its elevated expression is correlated with poor clinical outcome. European journal of cancer (Oxford, England : 1990) 59 23063350
2004 ARK5 expression in colorectal cancer and its implications for tumor progression. The American journal of pathology 59 14982852
2016 microRNA-203 suppresses invasion and epithelial-mesenchymal transition induction via targeting NUAK1 in head and neck cancer. Oncotarget 57 26882562
2019 miR-424-5p represses the metastasis and invasion of intrahepatic cholangiocarcinoma by targeting ARK5. International journal of biological sciences 52 31360102
2014 miR‑96 functions as a tumor suppressor gene by targeting NUAK1 in pancreatic cancer. International journal of molecular medicine 50 25242509
2014 Discovery of 8-cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a potent inhibitor of cyclin-dependent kinase 4 (CDK4) and AMPK-related kinase 5 (ARK5). Journal of medicinal chemistry 49 24417566
2020 Localized Inhibition of Protein Phosphatase 1 by NUAK1 Promotes Spliceosome Activity and Reveals a MYC-Sensitive Feedback Control of Transcription. Molecular cell 46 32006464
2016 ARK5 promotes doxorubicin resistance in hepatocellular carcinoma via epithelial-mesenchymal transition. Cancer letters 46 27126361
2015 Activation of ARK5/miR-1181/HOXA10 axis promotes epithelial-mesenchymal transition in ovarian cancer. Oncology reports 45 26151663
2004 Strong association of ARK5 with tumor invasion and metastasis. Journal of experimental & clinical cancer research : CR 43 15354411
2011 ARK5 is associated with the invasive and metastatic potential of human breast cancer cells. Journal of cancer research and clinical oncology 42 22105900
2019 MiR-204 inhibits hepatocellular cancer drug resistance and metastasis through targeting NUAK1. Biochemistry and cell biology = Biochimie et biologie cellulaire 40 30807203
2020 Dual targeting of NUAK1 and ULK1 using the multitargeted inhibitor MRT68921 exerts potent antitumor activities. Cell death & disease 35 32873786
2017 Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 28662499
2012 Muscle-specific knock-out of NUAK family SNF1-like kinase 1 (NUAK1) prevents high fat diet-induced glucose intolerance. The Journal of biological chemistry 33 22418434
2012 Neural tube defects by NUAK1 and NUAK2 double mutation. Developmental dynamics : an official publication of the American Association of Anatomists 32 22689267
2017 Calcium signalling links MYC to NUAK1. Oncogene 30 29106388
2020 A novel role for NUAK1 in promoting ovarian cancer metastasis through regulation of fibronectin production in spheroids. Cancers 29 32429240
2015 MiR-145 functions as a tumor suppressor targeting NUAK1 in human intrahepatic cholangiocarcinoma. Biochemical and biophysical research communications 29 26255969
2006 NDR2 acts as the upstream kinase of ARK5 during insulin-like growth factor-1 signaling. The Journal of biological chemistry 29 16488889
2018 Haploinsufficiency of autism spectrum disorder candidate gene NUAK1 impairs cortical development and behavior in mice. Nature communications 28 30327473
2016 Dual Targeting of CDK4 and ARK5 Using a Novel Kinase Inhibitor ON123300 Exerts Potent Anticancer Activity against Multiple Myeloma. Cancer research 28 26873845
2014 Interplay between Polo kinase, LKB1-activated NUAK1 kinase, PP1βMYPT1 phosphatase complex and the SCFβTrCP E3 ubiquitin ligase. The Biochemical journal 26 24785407
2025 Targeting the mevalonate pathway potentiates NUAK1 inhibition-induced immunogenic cell death and antitumor immunity. Cell reports. Medicine 24 39824180
2024 The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions. Nature communications 24 38514619
2020 miR-622 is a novel potential biomarker of breast carcinoma and impairs motility of breast cancer cells through targeting NUAK1 kinase. British journal of cancer 23 32418991
2021 NUAK1 and NUAK2 Fine-Tune TGF-β Signaling. Cancers 22 34282782
2020 Cytosolic NUAK1 Enhances ATP Production by Maintaining Proper Glycolysis and Mitochondrial Function in Cancer Cells. Frontiers in oncology 21 32754444
2017 Inhibition of AMPK-related kinase 5 (ARK5) enhances cisplatin cytotoxicity in non-small cell lung cancer cells through regulation of epithelial-mesenchymal transition. American journal of translational research 20 28469776
2021 MicroRNA-1182 and let-7a exert synergistic inhibition on invasion, migration and autophagy of cholangiocarcinoma cells through down-regulation of NUAK1. Cancer cell international 19 33750398
2019 Identification of a nuclear localization signal and importin beta members mediating NUAK1 nuclear import inhibited by oxidative stress. Journal of cellular biochemistry 19 31090959
2019 LINC00958 Promotes The Malignancy Of Nasopharyngeal Carcinoma By Sponging microRNA-625 And Thus Upregulating NUAK1. OncoTargets and therapy 18 31819474
2022 Loss of LKB1-NUAK1 signalling enhances NF-κB activity in a spheroid model of high-grade serous ovarian cancer. Scientific reports 17 35194062
2021 Role of ARK5 in cancer and other diseases (Review). Experimental and therapeutic medicine 16 33986861
2017 Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 15 28832761
2024 NUAK1 activates STAT5/GLI1/SOX2 signaling to enhance cancer cell expansion and drives chemoresistance in gastric cancer. Cell reports 14 38996065
2024 NUAK1-Mediated Phosphorylation of NADK Mitigates ROS Accumulation to Promote Osimertinib Resistance in Non-Small Cell Lung Carcinoma. Cancer research 14 39159134
2023 NUAK1 governs centrosome replication in pancreatic cancer via MYPT1/PP1β and GSK3β-dependent regulation of PLK4. Molecular oncology 14 36975767
2021 LINC00922 promotes the proliferation, migration, invasion and EMT process of liver cancer cells by regulating miR-424-5p/ARK5. Molecular and cellular biochemistry 14 34097192
2020 LncRNA NEAT1/miR-204/NUAK1 Axis is a Potential Therapeutic Target for Non-Small Cell Lung Cancer. Cancer management and research 14 33402847
2018 AMPK-related kinase 5 (ARK5) enhances gemcitabine resistance in pancreatic carcinoma by inducing epithelial-mesenchymal transition. American journal of translational research 14 30662653
2018 NUAK1 knockdown suppresses prostate cancer cell epithelial-mesenchymal transition, migration, and invasion through microRNA-30b-5p. International journal of clinical and experimental pathology 13 31949655
2023 LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression. Journal of Cancer 12 37576402
2011 Identification and prioritization of NUAK1 and PPP1CC as positional candidate loci for skeletal muscle strength phenotypes. Physiological genomics 11 21750233
2023 Inhibition of growth and contraction in human prostate stromal cells by silencing of NUAK1 and -2, and by the presumed NUAK inhibitors HTH01-015 and WZ4003. Frontiers in pharmacology 10 37188272
2023 NUAK1 coordinates growth factor-dependent activation of mTORC2 and Akt signaling. Cell & bioscience 10 38135881
2020 Yeast Nuak1 phosphorylates histone H3 threonine 11 in low glucose stress by the cooperation of AMPK and CK2 signaling. eLife 10 33372657
2024 ARK5 enhances cell survival associated with mitochondrial morphological dynamics from fusion to fission in human multiple myeloma cells. Cell death discovery 9 38282096
2023 NUAK1 promotes tumor metastasis through upregulating slug transcription in esophageal squamous cell carcinoma. Cancer cell international 9 37919754
2022 Discovery of a novel NUAK1 inhibitor against pancreatic cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 8 35691157
2017 ARK5 promotes invasion and migration in hepatocellular carcinoma cells by regulating epithelial-mesenchymal transition. Oncology letters 8 29434843
2014 Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head. The International journal of developmental biology 8 25354459
2024 NUAK1 promotes metabolic dysfunction-associated steatohepatitis progression by activating Caspase 6-driven pyroptosis and inflammation. Hepatology communications 6 38967580
2022 Enhanced Expression of ARK5 in Hepatic Stellate Cell and Hepatocyte Synergistically Promote Liver Fibrosis. International journal of molecular sciences 6 36361872
2022 DKK1 promotes NUAK1 transcriptional expression through the activation Akt in hepatocellular carcinoma. Cell biology international 6 36480792
2019 Knockdown of ARK5 expression suppresses invasion of ovarian cancer cells. Molecular medicine reports 6 30720082
2025 NUAK1 acts as a novel regulator of PD-L1 via activating GSK-3β/β-catenin pathway in hepatocellular carcinoma. Molecular medicine (Cambridge, Mass.) 5 39901136
2024 Discovery of UCB9386: A Potent, Selective, and Brain-Penetrant Nuak1 Inhibitor Suitable for In Vivo Pharmacological Studies. Journal of medicinal chemistry 5 39588908
2022 miR-622 Counteracts the NUAK1-Induced Gastric Cancer Cell Proliferation and the Antioxidative Stress. Disease markers 5 35872695
2020 WZ4003 sensitizes non-small cell lung cancer cells to gefitinib via inhibition of ARK5 and epithelial-to-mesenchymal transition. American journal of translational research 5 33312374
2017 Retraction: Wang, L., Ma, X., Yan, L., Wang, T., Wen, J. and Mi, G., LncRNA SNHG1 negatively regulates miR-145a-5p to enhance NUAK1 expression and promote cancer cell metastasis and invasion in nasopharyngeal carcinoma. J Cell Physiol. Accepted Author Manuscript. doi:10.1002/jcp.26340. Journal of cellular physiology 5 29215719
2024 1,2-bis(2,4,6-tribromophenoxy) ethane induces necroptosis via the co-competition of GAS5 and NUAK1 for miR-743a-5p in rat hepatocytes. Journal of hazardous materials 4 39141942
2022 AMPK-related protein kinase ARK5 regulates subcellular localization of RNA-binding protein hnRNP A1 during hypertonic stress. The Journal of biological chemistry 4 35963429
2022 Circ_0003998 upregulates ARK5 expression to elevate 5-Fluorouracil resistance in hepatocellular carcinoma through binding to miR-513a-5p. Anti-cancer drugs 4 36255069
2023 Evaluation of ARK5 and SIRT3 expression in renal cell carcinoma and their clinical significance. Diagnostic pathology 3 37996927
2021 [Role of miR-145-5p Targeting ARK5 in Regulating the Proliferation and Apoptosis of Human Epithelial Ovarian Cancer Cells]. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 3 34728027
2025 Development of the Pyrido[2,3-d]pyrimidin-7(8H)-one Scaffold toward Potent and Selective NUAK1 Inhibitors. ACS medicinal chemistry letters 2 39967649
2025 Ubiquitin Specific Protease 9X Regulates the Activation of ARK5 and Promotes Progression of Fibrotic Remodeling. JACC. Basic to translational science 2 40310323
2025 NUAK1 Promotes Diabetic Kidney Disease by Accelerating Renal Tubular Senescence via the ROS/P53 Axis. Diabetes 2 41264843
2020 Silencing of the ARK5 gene reverses the drug resistance of multidrug-resistant SGC7901/DDP gastric cancer cells. PeerJ 2 32844054
2025 Functional characterization of key protein biomarkers in spontaneous intracerebral hemorrhage pathogenesis: Structure and function of NUAK1 protein and ERO1L protein macromolecules. International journal of biological macromolecules 1 40203915
2020 Splice or Die: When MYC Is Driving, Transcription Needs NUAK1 to Avoid Fatal Pileups. Molecular cell 1 32200795
2026 NUAK1 silencing enhances radiotherapy-induced ferroptosis in locally advanced rectal cancer by impairing Nrf2-driven transcription of GPX4. Cellular oncology (Dordrecht, Netherlands) 0 41848996
2026 Structure-Based Design of Potent and Highly Selective NUAK1 Inhibitors by Exploiting a Unique Glutamate Switch for the Prevention of Tumor Growth, Migration, and Invasion. Journal of medicinal chemistry 0 41855469
2026 Epigenetic inhibition of class I histone deacetylases by MS-275 attenuates diabetic skeletal muscle atrophy via Akt/ARK5-FoxO and myostatin-Smad signaling. Frontiers in endocrinology 0 41877927
2026 Chemical Genetic Screen Identifies PSD3 as a Direct Substrate of NUAK1 that Regulates Dendritic Spine Maturation. bioRxiv : the preprint server for biology 0 42079242
2026 Advanced nanoformulations of NUAK1 regulate NLRP3 inflammasome for preeclampsia management in mice. Nature communications 0 42151142
2025 WZ4003 sensitizes hepatocellular carcinoma to OSI-027 by inhibiting ARK5-mediated autophagy. Cancer letters 0 40834984
2025 Development of Purine and Pyrrolopyrimidine Scaffolds as Potent, Selective, and Brain Penetrant NUAK1 Inhibitors. ACS medicinal chemistry letters 0 41257021
2025 Plasmodium falciparum exploits NUAK1 to establish infection in human erythrocytes. bioRxiv : the preprint server for biology 0 41278793
2016 [Construction of a RNAi lentiviral vector targeting ARK5 gene and its effect on the biological behavior of gastric cancer SGC7901 cells]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 0 26899327

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