Affinage

Showing MAPK8 — JNK is a alias.

MAPK8

Mitogen-activated protein kinase 8 · UniProt P45983

Length
427 aa
Mass
48.3 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 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

MAPK8/JNK1 is a stress-activated serine/threonine kinase that integrates diverse upstream signals into the phosphorylation of substrates governing apoptosis, transcription, cytoskeletal dynamics, cell-cycle progression, and tissue-specific physiology (PMID:9889102, PMID:11062067, PMID:12818176). Full activation requires dual phosphorylation of its Thr-Pro-Tyr activation motif, with MKK4 preferentially modifying Tyr-185 and MKK7 preferentially modifying Thr-183, so that the two upstream kinases act synergistically across JNK isoforms (PMID:9889102, PMID:11062067). The kinase is fed by multiple upstream modules — HPK1 acting through MLK-3 and MKK4 (PMID:9003777), PKG via direct MEKK1 phosphorylation (PMID:11278263), Sef through a TAK1–MKK4 route (PMID:15277532), and PKC acting through the RACK1 adaptor to phosphorylate JNK on Ser129, which primes subsequent MKK4/MKK7 activation (PMID:16061178). JNK activity is restrained by the inhibitor GSTp, which dissociates upon oxidative stress to relieve inhibition (PMID:10064598), by glucocorticoid receptor binding that displaces JNK from MKK7 (PMID:14609950), and is sustained at the protein level by the deubiquitinase USP14 (PMID:36693850). Among its effectors, JNK phosphorylates the transcription factor axis and apoptotic machinery, including BIM(EL) at Ser65 to potentiate proapoptotic activity (PMID:12818176), BNIP3 at Ser60/Thr66 to license LC3-dependent mitophagy (PMID:36396625), Bcl-2 to release Beclin1 and drive autophagy (PMID:31295022), SIRT1 at Ser27/Ser47/Thr530 to enhance its nuclear deacetylase activity (PMID:20027304), Hes-1 at Ser263 to repress GluR1 transcription in neurons (PMID:22302822), the cytoskeletal regulators paxillin at Ser178 for rapid cell migration (PMID:12853963) and SCG10 at Ser62/Ser73 to control axodendritic length (PMID:16618812), and the cell-cycle regulator Cdh1, establishing reciprocal control with the APC/C that also degrades nuclear JNK (PMID:20581839). At the organismal level, JNK1 directs TH cell proliferation, apoptosis, and TH2 differentiation (PMID:9851932), guides region-specific apoptosis in brain development (PMID:10230788), protects against hepatic steatosis (PMID:19945406), drives hepatocyte lipoapoptosis through PUMA induction (PMID:19638343), supports platelet secretion and thrombus formation (PMID:20231429), and restrains antifungal immunity via NFATc1-dependent CD23 suppression (PMID:28112734). Loss of JNK signaling in breast epithelium produces genomic instability and tumor initiation, defining JNK as a tumor suppressor (PMID:29856313).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1996 Medium

    Identifying HPK1 as a selective upstream activator established that JNK is engaged through a defined MLK-3/MKK4 kinase cascade distinct from the ERK and p38 pathways.

    Evidence Transfection in COS1 cells with pathway-specific kinase assays and dominant-negative epistasis

    PMID:9003777

    Open questions at the time
    • Physiological stimuli engaging HPK1 to JNK not defined
    • Single cell-based overexpression system
  2. 1998 High

    Mapping the dual-specificity input resolved how JNK reaches full activity: MKK4 and MKK7 phosphorylate distinct residues of the activation loop and act synergistically.

    Evidence In vitro kinase assays with site-specific phosphorylation mapping, extended across JNK isoforms

    PMID:11062067 PMID:9889102

    Open questions at the time
    • In vivo stoichiometry of dual phosphorylation not addressed
    • Functional consequence of MKK7-mediated Thr-404/Ser-407 phosphorylation unclear
  3. 1998 High

    Jnk1 knockout T cells defined a physiological role in adaptive immunity, showing JNK1 restrains proliferation and biases TH differentiation toward TH2.

    Evidence Jnk1-/- mouse T cell activation, cytokine profiling, and NFATc localization assays

    PMID:9851932

    Open questions at the time
    • Direct JNK1 substrates controlling NFATc accumulation not identified
    • Isoform redundancy with JNK2 not resolved
  4. 1999 High

    Discovery of GSTp as a dissociable inhibitor established a redox-gated brake on JNK independent of the MEKK1-MKK4 module.

    Evidence Protein purification, Co-IP, in vitro kinase assays, and GSTp-null MEF complementation

    PMID:10064598

    Open questions at the time
    • Structural basis of GSTp oligomerization-driven release not defined
  5. 1999 High

    Compound knockouts showed JNK1 and JNK2 jointly govern region-specific apoptosis essential for brain morphogenesis.

    Evidence Single and compound Jnk knockout mice with histology and caspase activation assays

    PMID:10230788

    Open questions at the time
    • Effector substrates mediating region-specific death not identified
    • Mechanism of opposing forebrain vs hindbrain effects unknown
  6. 2003 High

    Substrate-level studies connected JNK to cell migration and apoptosis: phosphorylation of paxillin Ser178 enables labile adhesions, and BIM(EL) Ser65 phosphorylation potentiates the mitochondrial death pathway.

    Evidence In vitro kinase assays, site mutagenesis, migration assays, and subcellular fractionation

    PMID:12818176 PMID:12853963

    Open questions at the time
    • Spatial control of mitochondrial vs cytoskeletal JNK pools not fully resolved
  7. 2003 High

    Glucocorticoid receptor binding was shown to inhibit JNK by displacing it from MKK7, defining a hormone-regulated docking mechanism that loads inactive JNK onto AP-1 elements.

    Evidence Co-IP, domain mapping, ChIP, and inactive-JNK nuclear transfer assays

    PMID:14609950

    Open questions at the time
    • Generality of inactive-JNK promoter loading across genes not established
  8. 2005 High

    Identification of RACK1-dependent PKC phosphorylation of JNK Ser129 revealed a priming step required for activation by specific stimuli.

    Evidence Co-IP, Ser129 mutagenesis, RACK1 siRNA, and in vitro kinase assays across multiple stimuli

    PMID:16061178

    Open questions at the time
    • Structural mechanism by which Ser129 priming augments MKK activation unknown
  9. 2006 High

    In vivo identification of SCG10 as a JNK1 substrate linked the kinase to neuronal microtubule dynamics and axodendritic architecture.

    Evidence Affinity purification, in vivo phospho-site mapping, JNK1-/- cortex analysis, FRAP, and neurite assays

    PMID:16618812

    Open questions at the time
    • Contribution relative to other stathmin-family regulators not quantified
  10. 2009 High

    JNK1 was shown to physically engage and phosphorylate SIRT1 under oxidative stress, enhancing its nuclear localization and substrate-selective deacetylase activity.

    Evidence Endogenous Co-IP, in vitro kinase with site mapping, nuclear fractionation, and deacetylase assays

    PMID:20027304

    Open questions at the time
    • Basis for SIRT1 substrate switching (H3 vs p53) not mechanistically defined
  11. 2009 High

    Tissue-specific and isoform-specific knockouts revealed opposing roles in liver: hepatic JNK1 protects against steatosis while driving lipoapoptosis via PUMA, and JNK2 restrains Bim/Bax-dependent injury.

    Evidence Hepatocyte-specific and global Jnk knockouts, ChIP/EMSA, antisense knockdown, and metabolic readouts

    PMID:19053047 PMID:19638343 PMID:19945406

    Open questions at the time
    • Reconciliation of protective vs proapoptotic hepatic JNK1 roles incomplete
    • Cell-type origin of opposing effects not fully delineated
  12. 2010 High

    Reciprocal regulation between JNK and APC/C(Cdh1) was established: APC/C degrades nuclear JNK during mitotic exit while JNK phosphorylates Cdh1 to attenuate APC/C in G2/M, integrating JNK into cell-cycle control.

    Evidence Co-IP, fractionation, in vitro kinase, non-degradable JNK mutant, and synchronization assays

    PMID:20581839

    Open questions at the time
    • Cell-cycle phenotype of preventing JNK degradation not fully characterized
  13. 2010 High

    Jnk1 knockout established a role in hemostasis, with JNK1 required for platelet secretion, integrin activation, and thrombus formation via PKC.

    Evidence Jnk1-/- platelets, aggregation/secretion assays, bleeding time, and in vivo thrombosis models

    PMID:20231429

    Open questions at the time
    • Platelet JNK1 substrates driving secretion not identified
  14. 2012 Medium

    JNK was placed in autophagy regulation downstream of TRAF2/RIPK1, mediating Bcl-xL degradation and BCL2L1-BECN1 dissolution to enable cytoprotective autophagy.

    Evidence siRNA of TRAF2/RIPK1/BECN1/ATG7 with autophagy and apoptosis readouts in cancer lines

    PMID:23051914

    Open questions at the time
    • Direct JNK phosphorylation event triggering Bcl-xL degradation not mapped
    • Single-lab pathway ordering
  15. 2012 High

    Phosphorylation of Hes-1 at Ser263 defined a transcriptional mechanism by which JNK1 represses GluR1 and dampens AMPA-evoked calcium signaling in neurons.

    Evidence In vitro kinase, Ser263 mutagenesis, promoter reporter, ChIP, and calcium imaging

    PMID:22302822

    Open questions at the time
    • Physiological context driving this pathway in vivo not established
  16. 2017 High

    JNK1 was shown to suppress antifungal immunity by limiting NFATc1-driven CD23 expression and CD23-dependent nitric oxide production.

    Evidence Jnk1-/- mice, bone marrow chimeras, CD23 promoter reporters, and NO measurement

    PMID:28112734

    Open questions at the time
    • Direct JNK1 substrate controlling NFATc1-CD23 axis not identified
  17. 2018 High

    Mammary-specific JNK deletion defined JNK as a tumor suppressor acting through genome stability to prevent tumor initiation rather than restrain established growth.

    Evidence Mammary epithelium-specific JNK knockout mice with genomic instability and tumor incidence assays

    PMID:29856313

    Open questions at the time
    • Molecular substrates linking JNK to genome stability not defined
  18. 2022 High

    JNK1/2 phosphorylation of BNIP3 at Ser60/Thr66 was shown to stabilize BNIP3 and promote LC3-dependent mitophagy under hypoxia, with PP1/2A reversing the modification.

    Evidence In vitro kinase, site mutagenesis, BNIP3-LC3 Co-IP, proteasome inhibition, and mitophagy assays

    PMID:36396625

    Open questions at the time
    • Relative contribution of JNK1 vs JNK2 not separated
    • Single-lab study
  19. 2023 Medium

    USP14 was identified as a deubiquitinase that binds and stabilizes JNK protein, sustaining pathway output.

    Evidence Co-IP, knockdown/knockout in vitro and in vivo, and ubiquitination Western blots

    PMID:36693850

    Open questions at the time
    • Direct deubiquitination of JNK not biochemically reconstituted
    • Specific ubiquitin chain/site removed not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How JNK1 isoform- and tissue-specific outputs are encoded — the rules selecting among apoptotic, autophagic, cytoskeletal, transcriptional, and tumor-suppressive substrates in a given context — remains unresolved.
  • No unifying model linking scaffold/upstream input to substrate choice
  • Distinct JNK1 vs JNK2 substrate repertoires incompletely defined
  • Spatial control of JNK substrate pools not systematically mapped

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 7 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-5357801 Programmed Cell Death 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 3 R-HSA-168256 Immune System 2 R-HSA-1640170 Cell Cycle 1
Partners
BNIP3CDH1GSTPMKK4MKK7RACK1SIRT1USP14

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 GSTp (glutathione S-transferase Pi) was purified and identified as a JNK-associated inhibitor protein. Monomeric GSTp inhibits JNK activity in a dose-dependent manner; UV irradiation or H2O2 treatment causes GSTp oligomerization and dissociation of the GSTp-JNK complex, relieving inhibition. GSTp inhibition of JNK is independent of the MEKK1-MKK4 module. Protein purification, co-immunoprecipitation, in vitro kinase assay with purified GSTp, immunodepletion, forced expression/cDNA complementation in GSTp-null MEFs The EMBO journal High 10064598
1998 MKK4 and MKK7 synergistically activate SAPK1/JNK1 in vitro: MKK4 preferentially phosphorylates the tyrosine residue (Tyr-185) and MKK7 preferentially phosphorylates the threonine residue (Thr-183) within the Thr-Pro-Tyr activation motif, such that both kinases together produce synergistic activation. In vitro kinase assay, site-specific phosphorylation analysis Current biology : CB High 11062067 9889102
2000 MKK4 shows striking preference for phosphorylation of Tyr-185, and MKK7 shows striking preference for Thr-183 in JNK1α1, JNK2α2, and JNK3α1 isoforms, producing synergistic activation when combined. MKK7 also phosphorylates JNK2α2 at Thr-404 and Ser-407 in vitro and in cells. In vitro kinase assay with three SAPK1/JNK isoforms, phospho-specific immunoblotting in KB cells and HEK-293 cells The Biochemical journal High 11062067
2003 JNK1 phosphorylates paxillin at Ser178 both in vitro and in intact cells. Expression of the Ser178→Ala paxillin mutant inhibited rapid cell migration in fish keratocytes and NBT-II cells, blocking the labile adhesions required for rapid movement. In vitro kinase assay, site-directed mutagenesis, single-cell migration and wound-healing assays Nature High 12853963
2003 JNK phosphorylates BIM(EL) at Ser65, potentiating its proapoptotic activity. Mitochondrially localized JNK specifically phosphorylates BIM(EL), whereas upstream activators (MLKs, MKKs) do not. This phosphorylation both promotes BIM(EL) expression transcriptionally and increases its proapoptotic activity posttranslationally. In vitro kinase assay, site-directed mutagenesis (Ser65), subcellular fractionation, loss-of-function JNK pathway inhibition with functional apoptosis readouts Neuron High 12818176
2005 RACK1 serves as an adaptor for PKC-mediated JNK activation. PKC phosphorylates JNK on Ser129 in a RACK1-dependent manner; Ser129 phosphorylation augments subsequent JNK phosphorylation by MKK4/MKK7 and is required for JNK activation by TPA, TNFα, UV irradiation, and PKC, but not by anisomycin or MEKK1. Co-immunoprecipitation, site-directed mutagenesis (Ser129), siRNA knockdown of RACK1, in vitro kinase assay Molecular cell High 16061178
2006 JNK1 phosphorylates SCG10 (a stathmin-family microtubule-destabilizing protein) in vivo at Ser62 and Ser73, regulating its microtubule-depolymerizing activity. SCG10-S73 phosphorylation is significantly decreased in JNK1-/- cortex. JNK1 phosphorylation of SCG10 determines axodendritic length in cerebrocortical cultures. Affinity purification of JNK-interacting proteins from brain, in vivo phosphorylation with phospho-site mapping, JNK1-/- mouse cortex analysis, FRAP (fluorescent tubulin recovery), neurite length assays The Journal of cell biology High 16618812
2009 JNK1 physically interacts with SIRT1 under oxidative stress conditions (co-immunoprecipitation of endogenous proteins). JNK1 phosphorylates SIRT1 at Ser27, Ser47, and Thr530, increasing SIRT1 nuclear localization and enzymatic activity with substrate specificity: phosphorylated SIRT1 deacetylates histone H3 but not p53. Co-immunoprecipitation of endogenous proteins, in vitro kinase assay, site-directed mutagenesis, nuclear fractionation, SIRT1 enzymatic activity assay, RNAi PloS one High 20027304
2010 Nuclear-localized JNK is degraded by the APC/C(Cdh1) ubiquitin ligase during exit from mitosis and G1 phase. Conversely, JNK phosphorylates Cdh1 during G2 and early mitosis, changing Cdh1 subcellular localization and attenuating its ability to activate the APC/C during G2/M. Co-immunoprecipitation, subcellular fractionation, in vitro kinase assay, expression of non-degradable JNK mutant, cell cycle synchronization Nature cell biology High 20581839
1996 HPK1 (hematopoietic progenitor kinase 1) specifically activates the SAPK/JNK pathway after transfection, acting via the SH3-containing mixed lineage kinase MLK-3 and the known SAPK activator SEK1 (MKK4). HPK1 does not stimulate p38/RK or ERK pathways. Transfection into COS1 cells, pathway-specific kinase activity assays, epistasis with dominant-negative pathway components The EMBO journal Medium 9003777
2001 Protein kinase G (PKG) activates JNK1 through a PKG-MEKK1-SEK1-JNK1 pathway by directly phosphorylating MEKK1. A dominant-negative MEKK1 inhibited PKG-induced JNK1 activation and c-Jun transactivation. In vitro assays showed purified PKG directly phosphorylated the N-terminal domain of MEKK1. In vitro kinase assay with purified PKG and MEKK1, constitutively active PKG mutant expression, dominant-negative MEKK1 epistasis, AP-1 reporter assay The Journal of biological chemistry Medium 11278263
2003 Glucocorticoid receptor (GR) inhibits JNK activation by physically associating with JNK upon glucocorticoid treatment, promoting disassembly of JNK from MKK7. A hormone-regulated JNK docking site was characterized in the GR ligand-binding domain. GC-induced GR-JNK association correlates with increased loading of inactive JNK on AP-1-bound response elements of the c-jun gene. Co-immunoprecipitation, domain mapping mutagenesis, chromatin immunoprecipitation (ChIP), inactive JNK nuclear transfer assays The EMBO journal High 14609950
1998 JNK1 signaling is required for T cell receptor-initiated TH cell proliferation, apoptosis, and differentiation. Jnk1-/- T cells hyperproliferate, show decreased activation-induced cell death, and preferentially differentiate to TH2 cells. Enhanced TH2 cytokine production is associated with increased nuclear accumulation of NFATc. Jnk1 knockout mouse analysis, T cell activation assays, cytokine profiling, NFATc nuclear localization assay Science High 9851932
1999 Jnk1 and Jnk2 are jointly required for region-specific apoptosis during early brain development. Jnk1/Jnk2 double-knockout compound mutants are embryonic lethal with severe dysregulation of apoptosis: reduced cell death in lateral hindbrain and increased apoptosis/caspase activation in forebrain. Jnk1-/-, Jnk2-/-, Jnk3-/- single and compound knockout mice, histological analysis, caspase activation assays Neuron High 10230788
2007 JNK1-dependent PUMA expression contributes to hepatocyte lipoapoptosis. Palmitate induction of PUMA is JNK1-dependent in primary murine hepatocytes; phosphorylated c-Jun in an AP-1 complex directly binds the PUMA promoter as shown by EMSA and ChIP. PUMA knockdown attenuated Bax activation, caspase 3/7 activity, and cell death. JNK1 knockout primary hepatocytes, dominant-negative c-Jun, EMSA, chromatin immunoprecipitation (ChIP), shRNA knockdown, caspase activity assays The Journal of biological chemistry High 19638343
2009 Hepatic JNK1 prevents steatosis: mice with specific ablation of Jnk1 in hepatocytes develop glucose intolerance, insulin resistance, and hepatic steatosis, demonstrating that JNK1 serves opposing actions in liver versus adipose tissue. Hepatocyte-specific Jnk1 conditional knockout mice, glucose tolerance tests, insulin sensitivity assays, histological analysis of liver Cell metabolism High 19945406
2009 JNK2-deficient mice on high-fat diet show increased liver injury through a Bim-dependent activation of the mitochondrial death pathway. JNK2 ablation increases hepatic expression of proapoptotic Bcl-2 family members Bim and Bax, revealing that JNK1 and JNK2 have distinct isoform-specific effects on steatohepatitis. Jnk1-/- and Jnk2-/- knockout mice, antisense oligonucleotide knockdown, high-fat diet model, Western blot for apoptotic proteins, histological analysis Hepatology High 19053047
2022 JNK1/2 phosphorylates BNIP3 at Ser60/Thr66 under hypoxia, which hampers proteasomal degradation of BNIP3 and promotes mitophagy by facilitating direct binding of BNIP3 to LC3. PP1/2A dephosphorylates BNIP3 and triggers its proteasomal degradation, suppressing mitophagy. In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation (BNIP3-LC3), proteasome inhibitor assays, mitophagy readouts under hypoxia Cell death & disease High 36396625
2007 FDH-induced p53 phosphorylation at Ser6 is carried out by JNK1 and JNK2 cooperatively: JNK1 phosphorylates JNK2 first, and then JNK2 (but not JNK1) directly phosphorylates p53 at Ser6. Pull-down assay showed JNK2 but not JNK1 physically associates with p53. siRNA knockdown of JNK1 and JNK2, pharmacological inhibitor SP600125, pull-down assay, phospho-specific Western blot Oncogene Medium 17525747
2010 JNK1 is required for platelet secretion and thrombus formation in vivo. JNK1-/- platelets show impaired secretion at low agonist doses, leading to altered integrin αIIbβ3 activation and reduced platelet aggregation via a mechanism involving protein kinase C. In vivo, JNK1-/- mice show prolonged bleeding times and reduced thrombus formation. JNK1-/- knockout mice, tail-bleeding assay, whole-blood perfusion on collagen matrix, in vivo photochemical thrombosis model, in vitro platelet aggregation and secretion assays Blood High 20231429
2017 JNK1 suppresses antifungal immunity by inhibiting CD23 expression through NFATc1-mediated regulation of the CD23 gene promoter. JNK1 deficiency leads to higher CD23 induction, and CD23-dependent nitric oxide production mediates the enhanced antifungal response. JNK1-/- mice, bone marrow chimeras, CD23 promoter reporter assays, NFATc1 knockdown, nitric oxide measurement, pharmacological JNK inhibition Nature medicine High 28112734
2023 USP14 is a deubiquitinase that physically interacts with JNK and stabilizes it by removing ubiquitin modifications, thereby sustaining MAPK/JNK signaling. USP14 ablation reduces JNK protein levels and downstream pathway activation. Co-immunoprecipitation, RNA-seq, luciferase reporter assay, USP14 knockdown/knockout in vitro and in vivo, Western blot for ubiquitination Cell death & disease Medium 36693850
2012 TRAF2- and RIPK1-mediated MAPK8/JNK activation is required for TNFSF10/TRAIL-induced cytoprotective autophagy. MAPK8 activation mediates BCL2L1/Bcl-xL degradation and dissolution of the BCL2L1-BECN1 complex. Knockdown of TRAF2 or RIPK1 suppresses TNFSF10-induced MAPK8 activation and autophagy. siRNA knockdown of TRAF2, RIPK1, BECN1, ATG7; pharmacological inhibitors; apoptosis and autophagy assays in multiple cancer cell lines Autophagy Medium 23051914
2019 JNK1 regulates RANKL-induced osteoclastogenesis via a Bcl-2-Beclin1-autophagy pathway: RANKL induces JNK1-dependent phosphorylation of Bcl-2, which dissociates Beclin1 from the Bcl-2-Beclin1 complex to activate autophagy. JNK1 inhibition blocks this dissociation and increases apoptosis; Beclin1 overexpression rescues autophagy deficiency caused by JNK inhibition. Pharmacological JNK inhibitor (SP600125), RNA interference, Beclin1 overexpression rescue, Western blot for Bcl-2 phosphorylation, co-immunoprecipitation of Bcl-2-Beclin1 complex, autophagy and apoptosis assays FASEB journal Medium 31295022
2012 JNK1 inhibits GluR1 expression by phosphorylating Hes-1 at Ser263, stabilizing Hes-1 protein. Stabilized Hes-1 suppresses GluR1 promoter activity via N-box binding and by preventing Mash1/E47 from binding the E-box, ultimately inhibiting AMPA-evoked calcium influx in cortical neurons. In vitro kinase assay, site-directed mutagenesis (Ser263), promoter-reporter assay, chromatin immunoprecipitation, calcium imaging in cortical neurons The Journal of neuroscience High 22302822
2009 JNK1 determines whether integrin-linked kinase (ILK) functions as an oncogene or tumor suppressor in rhabdomyosarcoma. In ARMS cells, ILK depletion reduces JNK1/c-Jun signaling and suppresses growth; in ERMS cells, ILK depletion activates JNK1/c-Jun, promoting growth. Restoration of JNK1 in ARMS reestablishes a tumor-suppressive ILK function. RNAi-mediated ILK depletion, JNK1 restoration experiments, in vitro and in vivo growth assays, PAX3-FKHR expression in ERMS cells The Journal of clinical investigation Medium 19478459
2018 JNK pathway deficiency causes genomic instability and breast cancer development in mice. Loss of JNK signaling in breast epithelium leads to widespread early neoplasia and rapid tumor formation, identifying JNK as a tumor suppressor that prevents tumor initiation rather than controlling established tumor growth. Mammary epithelium-specific JNK knockout mice, breast cancer mouse model, genomic instability assays, tumor incidence and histological analysis eLife High 29856313
2004 Sef physically interacts with TAK1 and activates JNK through a TAK1-MKK4-JNK pathway. Dominant-negative forms of MKK4 and TAK1 blocked Sef-mediated JNK activation and attendant apoptosis. Co-immunoprecipitation, dominant-negative epistasis constructs (MKK4-DN, TAK1-DN), apoptosis assays The Journal of biological chemistry Medium 15277532
2008 Active (phosphorylated) MAPK8 colocalizes with BMF in testicular germ cells upon detachment from Sertoli cells; p-MAPK8 levels increase in round spermatids and spermatocytes undergoing apoptosis after Sertoli cell removal, suggesting MAPK8 activation and BMF redistribution mediate anoikis-like apoptosis of germ cells. Immunohistochemistry, Western blot for p-MAPK8/total MAPK8, immunocytochemistry of isolated germ cells in culture Journal of andrology Low 18222916

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 JNK signaling in apoptosis. Oncogene 1265 18931691
1999 Regulation of JNK signaling by GSTp. The EMBO journal 922 10064598
1994 MAPKs: new JNK expands the group. Trends in biochemical sciences 908 7855889
2007 The JNK signal transduction pathway. Current opinion in cell biology 894 17303404
1999 The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron 762 10230788
2002 The JNK signal transduction pathway. Current opinion in genetics & development 578 11790549
2003 Targeting JNK for therapeutic benefit: from junk to gold? Nature reviews. Drug discovery 506 12815381
1999 Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1. Cell 502 10367887
1998 Defective T cell differentiation in the absence of Jnk1. Science (New York, N.Y.) 502 9851932
2003 JNK-mediated BIM phosphorylation potentiates BAX-dependent apoptosis. Neuron 434 12818176
2003 JNK phosphorylates paxillin and regulates cell migration. Nature 412 12853963
2006 JNK- and Fos-regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila. The EMBO journal 335 17082773
2014 Nuclear and cytosolic JNK signalling in neurons. Nature reviews. Neuroscience 272 24739785
2010 JNK1 and IKKbeta: molecular links between obesity and metabolic dysfunction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 268 20371626
2007 The functional contrariety of JNK. Molecular carcinogenesis 229 17538955
2009 JNK1 phosphorylates SIRT1 and promotes its enzymatic activity. PloS one 224 20027304
2007 JNK signalling: a possible target to prevent neurodegeneration. Current pharmaceutical design 207 17584114
1996 HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway. The EMBO journal 205 9003777
2003 Role of JNK in tumor development. Cell cycle (Georgetown, Tex.) 195 12734425
2009 Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance. Hepatology (Baltimore, Md.) 189 19053047
2009 JNK1-dependent PUMA expression contributes to hepatocyte lipoapoptosis. The Journal of biological chemistry 166 19638343
2000 Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7. The Biochemical journal 164 11062067
1998 Synergistic activation of SAPK1/JNK1 by two MAP kinase kinases in vitro. Current biology : CB 164 9889102
2005 RACK1 mediates activation of JNK by protein kinase C [corrected]. Molecular cell 158 16061178
2007 JNK pathway: diseases and therapeutic potential. Acta pharmacologica Sinica 155 17439715
2006 JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length. The Journal of cell biology 154 16618812
2010 cJun NH2-terminal kinase 1 (JNK1): roles in metabolic regulation of insulin resistance. Trends in biochemical sciences 144 20452774
2009 JNK signalling modulates intestinal homeostasis and tumourigenesis in mice. The EMBO journal 140 19521338
2013 The 2 Faces of JNK Signaling in Cancer. Genes & cancer 137 24349637
2012 Attenuation of TNFSF10/TRAIL-induced apoptosis by an autophagic survival pathway involving TRAF2- and RIPK1/RIP1-mediated MAPK8/JNK activation. Autophagy 132 23051914
2009 Prevention of steatosis by hepatic JNK1. Cell metabolism 131 19945406
2008 Activation of JNK pathway in persistent pain. Neuroscience letters 128 18455869
2012 Role of the JNK pathway in human diseases. Progress in molecular biology and translational science 127 22340717
2007 Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene 116 17525747
2009 Correcting developmental errors by apoptosis: lessons from Drosophila JNK signaling. Apoptosis : an international journal on programmed cell death 112 19466550
2003 Glucocorticoid receptor-JNK interaction mediates inhibition of the JNK pathway by glucocorticoids. The EMBO journal 104 14609950
2010 Regulation of Drosophila lifespan by JNK signaling. Experimental gerontology 101 21111799
2010 The role of JNK proteins in metabolism. Science translational medicine 95 21123811
2004 NF-kappaB and JNK: an intricate affair. Cell cycle (Georgetown, Tex.) 93 15611622
2010 Platelet JNK1 is involved in secretion and thrombus formation. Blood 92 20231429
2017 JNK1 negatively controls antifungal innate immunity by suppressing CD23 expression. Nature medicine 86 28112734
2017 JNK, p38, ERK, and SGK1 Inhibitors in Cancer. Cancers 84 29267206
2022 BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia. Cell death & disease 82 36396625
2001 Protein kinase G activates the JNK1 pathway via phosphorylation of MEKK1. The Journal of biological chemistry 72 11278263
2005 Oxidative stress and the JNK pathway in diabetes. Current diabetes reviews 70 18220583
2021 JNK Pathway in CNS Pathologies. International journal of molecular sciences 68 33918666
2020 JNK signaling in Drosophila immunity and homeostasis. Immunology letters 67 32598968
2017 Hippo signaling promotes JNK-dependent cell migration. Proceedings of the National Academy of Sciences of the United States of America 67 28174264
2006 JNK regulation of oncogenesis. Molecules and cells 67 16682809
2009 Insulin and JNK: optimizing metabolic homeostasis and lifespan. Trends in endocrinology and metabolism: TEM 66 19251431
2004 JNK: a key modulator of intracellular signaling. Biochemistry. Biokhimiia 65 15377263
2019 Phosphorylation Dynamics of JNK Signaling: Effects of Dual-Specificity Phosphatases (DUSPs) on the JNK Pathway. International journal of molecular sciences 63 31817617
2021 The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases. International journal of molecular sciences 61 34502556
2009 JNK inhibition and inflammation after cerebral ischemia. Brain, behavior, and immunity 60 19903520
2018 The sucrose non-fermenting-1-related protein kinases SAPK1 and SAPK2 function collaboratively as positive regulators of salt stress tolerance in rice. BMC plant biology 59 30236054
1999 c-Jun functions as a calcium-regulated transcriptional activator in the absence of JNK/SAPK1 activation. The EMBO journal 59 10064599
2017 JNK pathway in osteoarthritis: pathological and therapeutic aspects. Journal of receptor and signal transduction research 58 28812968
2001 Reovirus infection activates JNK and the JNK-dependent transcription factor c-Jun. Journal of virology 56 11689607
2002 Targeting the JNK pathway for therapeutic benefit in CNS disease. Current drug targets. CNS and neurological disorders 53 12769633
2020 Alarmins and c-Jun N-Terminal Kinase (JNK) Signaling in Neuroinflammation. Cells 51 33114371
2000 Selective expression of JNK isoforms and stress-specific JNK activity in different neural cell lines. Brain research. Molecular brain research 49 10648896
2015 Fumonisin B1 induces autophagic cell death via activation of ERN1-MAPK8/9/10 pathway in monkey kidney MARC-145 cells. Archives of toxicology 48 25925693
2018 MAPK8 mediates resistance to temozolomide and apoptosis of glioblastoma cells through MAPK signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 47 30119215
2010 Interplay between Cdh1 and JNK activity during the cell cycle. Nature cell biology 47 20581839
2013 Network Motifs in JNK Signaling. Genes & cancer 45 24349639
1997 SKK4, a novel activator of stress-activated protein kinase-1 (SAPK1/JNK). FEBS letters 45 9305750
2012 JNK- and Akt-mediated Puma expression in the apoptosis of cisplatin-resistant ovarian cancer cells. The Biochemical journal 44 22394200
2019 JNK1 regulates RANKL-induced osteoclastogenesis via activation of a novel Bcl-2-Beclin1-autophagy pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 43 31295022
2021 JNK signaling as a target for anticancer therapy. Pharmacological reports : PR 41 33710509
2016 Glabridin induces apoptosis and autophagy through JNK1/2 pathway in human hepatoma cells. Phytomedicine : international journal of phytotherapy and phytopharmacology 41 27002406
2011 JNK-1 deficiency limits macrophage-mediated antigen-induced arthritis. Arthritis and rheumatism 41 21305529
2018 JNK Regulation of Depression and Anxiety. Brain plasticity (Amsterdam, Netherlands) 40 30151339
2013 Emerging role of JNK in insulin resistance. Current diabetes reviews 40 23865415
2016 JNK1/2 expression and modulation of STAT3 signaling in oral cancer. Oncology letters 39 27347203
2016 Food additives: Sodium benzoate, potassium sorbate, azorubine, and tartrazine modify the expression of NFκB, GADD45α, and MAPK8 genes. Physiology international 39 28229641
2019 JNK and cardiometabolic dysfunction. Bioscience reports 38 31270248
2009 JNK1 determines the oncogenic or tumor-suppressive activity of the integrin-linked kinase in human rhabdomyosarcoma. The Journal of clinical investigation 38 19478459
2008 ATF3 and Fra1 have opposite functions in JNK- and ERK-dependent DNA damage responses. DNA repair 38 18249159
2014 Crosstalk of JNK1-STAT3 is critical for RAW264.7 cell survival. Cellular signalling 37 25269780
2021 Recent Advances in c-Jun N-Terminal Kinase (JNK) Inhibitors. Current medicinal chemistry 36 32039671
2020 Inactivation of Hippo and cJun-N-terminal Kinase (JNK) signaling mitigate FUS mediated neurodegeneration in vivo. Neurobiology of disease 36 32199908
2014 JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis. PloS one 36 24475223
2004 Sef interacts with TAK1 and mediates JNK activation and apoptosis. The Journal of biological chemistry 36 15277532
2016 Localized JNK signaling regulates organ size during development. eLife 35 26974344
2009 JNK1, a potential therapeutic target for hepatocellular carcinoma. Biochimica et biophysica acta 35 19591900
2023 USP14 promotes colorectal cancer progression by targeting JNK for stabilization. Cell death & disease 34 36693850
2020 Brain JNK and metabolic disease. Diabetologia 33 33200240
2016 JNK1 Inhibition Attenuates Hypoxia-Induced Autophagy and Sensitizes to Chemotherapy. Molecular cancer research : MCR 33 27216154
2018 The cJUN NH2-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation. eLife 31 29856313
2013 JNK is a novel regulator of intercellular adhesion. Tissue barriers 31 24868495
2018 CtBP impedes JNK- and Upd/STAT-driven cell fate misspecifications in regenerating Drosophila imaginal discs. eLife 30 29372681
2019 TLR4 promotes liver inflammation by activating the JNK pathway. European review for medical and pharmacological sciences 29 31539158
2012 JNK1 inhibits GluR1 expression and GluR1-mediated calcium influx through phosphorylation and stabilization of Hes-1. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 22302822
2006 Players in the PARP-1 cell-death pathway: JNK1 joins the cast. Trends in biochemical sciences 29 16679020
2003 Synthetic anisomycin analogues activating the JNK/SAPK1 and p38/SAPK2 pathways. Organic & biomolecular chemistry 29 14737674
2020 Irreversible JNK1-JUN inhibition by JNK-IN-8 sensitizes pancreatic cancer to 5-FU/FOLFOX chemotherapy. JCI insight 28 32213714
2018 RhoA regulates Schwann cell differentiation through JNK pathway. Experimental neurology 28 29940159
2022 Diacerein protects liver against APAP-induced injury via targeting JNK and inhibiting JNK-mediated oxidative stress and apoptosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 36068777
2010 Preantral follicle growth is regulated by c-Jun-N-terminal kinase (JNK) pathway. Reproductive sciences (Thousand Oaks, Calif.) 27 20959642
2008 Phosphorylation of mitogen-activated protein kinase 8 (MAPK8) is associated with germ cell apoptosis and redistribution of the Bcl2-modifying factor (BMF). Journal of andrology 25 18222916

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