Property Summary

NCBI Gene PubMed Count 65
PubMed Score 60.65
PubTator Score 56.13

Knowledge Summary

Patent (5,176)


  Differential Expression (20)

Disease log2 FC p
Rheumatoid Arthritis 1.200 1.1e-02
gastric cancer 1.100 1.7e-03
hepatocellular carcinoma 1.200 1.4e-05
astrocytic glioma -2.000 3.6e-03
ependymoma -2.400 2.7e-03
oligodendroglioma -1.400 1.3e-02
psoriasis -1.100 3.3e-03
glioblastoma -2.600 1.4e-06
osteosarcoma -2.740 1.2e-08
atypical teratoid / rhabdoid tumor -2.400 8.6e-07
primitive neuroectodermal tumor -1.400 7.9e-03
adrenocortical carcinoma -1.084 1.6e-02
lung cancer 1.800 2.0e-04
Parkinson's disease -1.100 3.6e-02
pediatric high grade glioma -2.000 5.2e-06
sonic hedgehog group medulloblastoma -1.800 3.0e-04
pilocytic astrocytoma -1.700 1.0e-05
Pick disease -1.400 4.7e-03
acute myeloid leukemia -1.500 4.4e-02
ovarian cancer 1.400 3.3e-03

Protein-protein Interaction (8)

MLP Assay (1)

AID Type Active / Inconclusive / Inactive Description
1982 other 0 / 0 / 0 Kinase inhibition selectivity assay for compound SID-48409448

Gene RIF (42)

26823848 The expression of NLK was negatively correlated with TCF4 expression in lung cancers
26647877 Further experiments demonstrated that the overexpression of miR3623p resulted in decrease expression levels of nemo-like kinase
26588989 NLK phosphorylates Raptor on S863 to disrupt its interaction with the Rag GTPase, which is important for mTORC1 lysosomal recruitment.
26503628 NLK was involved in miR-92b-induced cell proliferation, and its protein level was obviously downregulated in the miR-92b-overexpressing xenograft tumors.
26503334 Data show that metformin inhibits nemo like kinase (NLK) expression and might be a potential treatment strategy for non-small cell lung cancer (NSCLC).
26427665 In this review, we will make a summary on the comprehensive roles of NLK in the regulation of various cancers
26269673 NLK overexpression is an independent prognostic factor in colorectal cancer and knockdown of NLK expression inhibits colorectal cancer progression and metastasis.
26252054 Down-regulation of NLK inhibited tumorigenesis and up-regulated the expression of cell cycle proteins in laryngeal cancer cells.
26022162 NLK overexpression is associated with poor overall survival in patients with hepatocellular carcinoma(HCC), it might be an independent poor prognostic marker for HCC.
25833695 our work first demonstrated that miR-197 can confer drug resistance to Taxol, by regulating tumor suppressor, NLK expression in ovarian cancer cells.
25512613 the TAK1-NLK pathway is a novel regulator of basal or IL-1beta-triggered C/EBP activation though stabilization of ATF5
24972723 NLK was an identified miR-199a-3p target gene and functioned as a tumor suppressor gene in colorectal cancer.
24926618 NLK is an important p53 regulator that responds to DNA damage. NLK interacts with p53 and stabilizes p53 by blocking MDM2-mediated p53 ubiquitination and degradation.
24816797 Data indicate that heat-shock protein 27 HSP27) binds to Nemo-like kinase (NLK) in the nucleus.
24721172 NLK functions as a pivotal negative regulator of NF-kappaB via disrupting the interaction of TAK1 with IKKbeta.
24460265 High nemo-like kinase expression is associated with drug resistance in laryngeal cancer.
23983589 The results suggest that NLK silencing by lentivirus-mediated RNA interference would be a potential therapeutic method to control oral squamous carcinoma growth.
23935942 NLK suppressed proliferation, induced apoptosis and mediated c-Myb degradation in MCF-7 cells.
23904219 NLK is a negative regulator in cell proliferation of non-small-cell lung cancer by modulating the activity of Wnt/beta-catenin signaling.
23857283 Data indicate that overexpression of nemo-like kinase (NLK) is closely related to progression of gallbladder cancer (GBC), and NLK could be used as a potential prognostic marker for GBC patients.
23416699 Reduced expression of NLK is associated with glioma.
23047923 In vitro protein-protein interaction analysis identifies a Vpu-binding host protein nemo-like kinase (NLK)
22733362 Our results suggested that NLK is a key regulator involved in proliferation and migration of GBC, and it could be used as a potential therapeutic target for gallbladder carcinoma cells.
22253297 Single nucleotide polymorphisms in NLK is associated with ovarian cancer.
22027747 expression suppressed in the development of ovarian cancer
21454679 ZIPK may serve as a transcriptional regulator of canonical Wnt/beta-catenin signaling through interaction with NLK/TCF4.
21177110 NLK induces apoptosis in glioma cells via activation of caspases; NLK may be a useful independent prognostic indicator for glioma.
21118996 dimerization is an initial key event required for the functional activation of NLK
20844743 Observational study of gene-disease association. (HuGE Navigator)
20512928 NLK is aberrantly regulated in hepatocellular carcinoma and this process appears to involve the induction of CDK2 and cyclin D1
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20118921 NLK negatively regulates Notch-dependent transcriptional activation by phosphorylating Notch1ICD. Phosphorylated Notch1ICD is impaired in its ability to form a transcriptionally active ternary complex.
20061393 findings provide the first evidence that TAK1-NLK pathway is a novel regulator of FOXO1
19690946 threonine 9 (Thr9) and Serine 138 (Ser138) within the N-terminal Mad homology1 (MH1) domain of Smad4 could be phosphorylated by NLK
19514049 NLK expression is altered during prostate cancer progression and it is involved in regulation of AR signaling in these cells
18765672 Fbxw7, the F-box protein of an SCF complex, targets c-Myb for degradation in a Wnt-1- and NLK-dependent manner.
17418100 These results strongly suggest that unlike cytokine signaling, Tax-induced NFkappaB activation does not involve K63 polyubiquitination-mediated MAP3K activation.
15764709 STAT3 enhances the efficiency of its own Ser-727 phosphorylation by acting as a scaffold for the TAK1-NLK kinases
14960582 Nemo-like kinase is activated by Wnt
12901858 The induction of wild-type NLK in DLD-1 human colon cancer cells caused suppression of cell growth whereas the kinase-negative mutant did not.
12556497 These results suggest that NLK phosphorylation on these sites contributes to the down-regulation of LEF-1/TCF transcriptional activity.
12482967 These results suggest that the TAK1-NLK MAPK cascade is activated by the noncanonical Wnt-5a/Ca(2+) pathway and antagonizes canonical Wnt/beta-catenin signaling.

AA Sequence

GNRVPLCINPQSAAFKSFISSTVAQPSEMPPSPLVWE                                     491 - 527

Text Mined References (72)

PMID Year Title
26823848 2015 Expression of Nemo-like kinase was increased and negatively correlated with the expression of TCF4 in lung cancers.
26647877 2016 miR-362-3p targets nemo-like kinase and functions as a tumor suppressor in renal cancer cells.
26588989 2015 NLK phosphorylates Raptor to mediate stress-induced mTORC1 inhibition.
26503628 2015 MicroRNA-92b promotes tumor growth and activation of NF-?B signaling via regulation of NLK in oral squamous cell carcinoma.
26503334 2015 NLK functions to maintain proliferation and stemness of NSCLC and is a target of metformin.
26427665 2015 The emerging role of Nemo-like kinase (NLK) in the regulation of cancers.
26269673 2015 Upregulation of nemo-like kinase is an independent prognostic factor in colorectal cancer.
26252054 2015 Lentivirus?delivered nemo?like kinase small interfering RNA inhibits laryngeal cancer cell proliferation in vitro.
26022162 2015 Prognostic significance of Nemo-like kinase expression in patients with hepatocellular carcinoma.
25833695 2015 MiR-197 induces Taxol resistance in human ovarian cancer cells by regulating NLK.
25512613 2015 Stabilization of ATF5 by TAK1-Nemo-like kinase critically regulates the interleukin-1?-stimulated C/EBP signaling pathway.
25416956 2014 A proteome-scale map of the human interactome network.
25241761 2014 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
24972723 2014 NLK, a novel target of miR-199a-3p, functions as a tumor suppressor in colorectal cancer.
24926618 2014 Nemo-like kinase is critical for p53 stabilization and function in response to DNA damage.
24816797 2014 Association of nuclear-localized Nemo-like kinase with heat-shock protein 27 inhibits apoptosis in human breast cancer cells.
24721172 2014 Nemo-like kinase (NLK) negatively regulates NF-kappa B activity through disrupting the interaction of TAK1 with IKK?.
24460265 2013 Inhibition of nemo-like kinase increases taxol sensitivity in laryngeal cancer.
23983589 2013 Lentivirus-based RNA silencing of Nemo-like kinase (NLK) inhibits the CAL 27 human adenosquamos carcinoma cells proliferation and blocks G0/G1 phase to S phase.
23935942 2013 Nemo-like kinase associated with proliferation and apoptosis by c-Myb degradation in breast cancer.
23904219 2014 Nemo-like kinase (NLK) inhibits the progression of NSCLC via negatively modulating WNT signaling pathway.
23857283 2013 Prognostic significance of nemo-like kinase (NLK) expression in patients with gallbladder cancer.
23602568 2013 The protein interaction landscape of the human CMGC kinase group.
23416699 2013 miR-92b controls glioma proliferation and invasion through regulating Wnt/beta-catenin signaling via Nemo-like kinase.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22773187 2012 Dual functions of DP1 promote biphasic Wnt-on and Wnt-off states during anteroposterior neural patterning.
22733362 2012 NLK is a key regulator of proliferation and migration in gallbladder carcinoma cells.
22253297 2012 Common variation in Nemo-like kinase is associated with risk of ovarian cancer.
22027747 2011 Expression of NLK and its potential effect in ovarian cancer chemotherapy.
21988832 2011 Toward an understanding of the protein interaction network of the human liver.
21516116 2011 Next-generation sequencing to generate interactome datasets.
21454679 2011 Zipper-interacting protein kinase (ZIPK) modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-like kinase and T-cell factor 4 (NLK/TCF4).
21177110 2011 Clinical and biological significance of nemo-like kinase expression in glioma.
21118996 2011 Homodimerization of Nemo-like kinase is essential for activation and nuclear localization.
20874444 2011 Oxidative stress-dependent regulation of Forkhead box O4 activity by nemo-like kinase.
20844743 2010 Single nucleotide polymorphisms in the Wnt and BMP pathways and colorectal cancer risk in a Spanish cohort.
20512928 2010 Targeted disruption of Nemo-like kinase inhibits tumor cell growth by simultaneous suppression of cyclin D1 and CDK2 in human hepatocellular carcinoma.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20118921 2010 Nemo-like kinase suppresses Notch signalling by interfering with formation of the Notch active transcriptional complex.
20061393 2010 Regulation of FOXO1 by TAK1-Nemo-like kinase pathway.
19690946 2010 Human SMAD4 is phosphorylated at Thr9 and Ser138 by interacting with NLK.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19514049 2009 Nemo-like kinase induces apoptosis and inhibits androgen receptor signaling in prostate cancer cells.
19369195 2009 Large-scale proteomics analysis of the human kinome.
19345186 2009 A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death.
18765672 2008 Fbxw7 acts as an E3 ubiquitin ligase that targets c-Myb for nemo-like kinase (NLK)-induced degradation.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17952062 2007 A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-gamma transactivation.
17513757 2007 Interaction of PRP4 with Kruppel-like factor 13 regulates CCL5 transcription.
17418100 2007 HTLV-1 Tax-induced NFkappaB activation is independent of Lys-63-linked-type polyubiquitination.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
16714285 2006 NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF).
16713569 2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15764709 2005 STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGFbeta-activated kinase 1 for STAT3 Ser-727 phosphorylation.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15308626 2004 Differential sensitivity of v-Myb and c-Myb to Wnt-1-induced protein degradation.
15082531 2004 Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK.
15004007 2004 Role of the TAK1-NLK-STAT3 pathway in TGF-beta-mediated mesoderm induction.
14960582 2004 Wnt activates the Tak1/Nemo-like kinase pathway.
14720327 2004 Nemo-like kinase suppresses a wide range of transcription factors, including nuclear factor-kappaB.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12901858 2003 Nemo-like kinase induces apoptosis in DLD-1 human colon cancer cells.
12556497 2003 Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphorylation in Wnt/beta-catenin signaling.
12482967 2003 The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12107411 2002 Expressed sequence tag analysis of human retina for the NEIBank Project: retbindin, an abundant, novel retinal cDNA and alternative splicing of other retina-preferred gene transcripts.
11707333 2001 Only one nemo-like kinase gene homologue in invertebrate and mammalian genomes.
10863097 2000 Characterization of the Fugu rubripes NLK and FN5 genes flanking the NF1 (Neurofibromatosis type 1) gene in the 5' direction and mapping of the human counterparts.
10524757 1998 Sequencing analysis of forty-eight human image cDNA clones similar to Drosophila mutant protein.
9448268 1998 Nlk is a murine protein kinase related to Erk/MAP kinases and localized in the nucleus.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.