Affinage

MAP3K7

Mitogen-activated protein kinase kinase kinase 7 · UniProt O43318

Length
606 aa
Mass
67.2 kDa
Annotated
2026-06-10
60 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP3K7 (TAK1) is a serine/threonine kinase that operates as a central signaling hub, transducing TGF-β, BMP, TNF, and cytokine inputs to activate downstream MAPK (p38, JNK, NLK) and NF-κB pathways through TAB1- and TAB2-dependent mechanisms (PMID:23226465, PMID:31668971). Its catalytic activation depends on autophosphorylation gated by an intact kinase domain and physical engagement of TAB1, with the activation-loop and ATP-binding residues being critical: disease variants that insert residues into the activation loop or substitute Val50 disrupt TAB1 binding and autophosphorylation, while gain-of-function mutations near the coiled-coil and kinase domains increase autophosphorylation (PMID:27426733, PMID:32105826, PMID:42040894). Kinase output is set by ubiquitin-dependent turnover — the E3 ligase TRIM31 catalyzes K48-linked polyubiquitination at Lys72 to drive proteasomal degradation and dampen TGF-β1–Smad/MAPK/NF-κB signaling — and by transcript availability, since SF3B1-mutant mis-splicing introduces a premature termination codon that triggers nonsense-mediated decay and depletes the kinase (PMID:34584221, PMID:34930825, PMID:33751071). Through these pathways MAP3K7 governs lineage-specific differentiation programs, including BMP-driven adipogenesis via synergy with TAB1 on PPARγ, erythroid maturation via a p38–GATA1 axis, and cardiac/endodermal specification (PMID:27293199, PMID:34930825, PMID:29281682, PMID:31668971). Bidirectional dysregulation produces distinct skeletal disorders: gain-of-function mutations cause frontometaphyseal dysplasia type 2, whereas loss-of-function mutations cause cardiospondylocarpofacial syndrome by impairing TGF-β–p38 signaling (PMID:27426733, PMID:27426734, PMID:32105826). In cancer, MAP3K7 controls androgen receptor protein levels through an IKKβ–βTRCP degradation route and acts as a cytoprotective checkpoint that restrains TNF/IFNγ-driven inflammatory cell death [PMID:34158377, PMID:bio_10.1101_2025.05.09.652721].

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2012 High

    Established that TAK1 activation in vivo requires TAB1/TAB2 adaptors and that TAK1 sustains hematopoietic stem cells both by blocking TNF-dependent death and through a TNF-independent maintenance route, defining the adaptor dependence and physiological output of the kinase.

    Evidence Conditional knockout of Tak1/Tab1/Tab2 with Tnfr1 epistasis and competitive transplantation in mice

    PMID:23226465

    Open questions at the time
    • Does not resolve the molecular nature of the TNF-independent maintenance pathway
    • Adaptor stoichiometry and direct activation mechanism not biochemically reconstituted
  2. 2012 Medium

    Delineated pathway specificity by showing activin A drives Fshb transcription through SMAD3/SMAD4 and NOT through TAK1 or p38, ruling out TAK1 in this gonadotrope context.

    Evidence Map3k7 siRNA, TAK1 inhibitor, and p38 phosphorylation negative controls in LβT2 cells

    PMID:22549017

    Open questions at the time
    • Negative result confined to a single cell type and promoter
    • Does not exclude TAK1 contribution to other activin-responsive genes
  3. 2013 High

    Positioned MAP3K7 within a Carma1–Bcl-10 immune signaling axis that selectively controls NK-cell cytokine production rather than cytotoxicity, distinguishing its functional outputs in immune effectors.

    Evidence Genetic epistasis across pathway nodes with dual cytotoxicity/cytokine readouts in NK cells

    PMID:24036998

    Open questions at the time
    • Direct substrates of MAP3K7 in this axis not identified
    • Mechanism segregating cytokine from cytotoxic output unresolved
  4. 2016 High

    Resolved that bidirectional MAP3K7 mutations cause opposite skeletal phenotypes — gain-of-function (increased autophosphorylation) drives frontometaphyseal dysplasia type 2 while loss-of-function impairs TGF-β–p38 signaling causing cardiospondylocarpofacial syndrome — linking kinase dosage to human disease.

    Evidence Whole-exome sequencing with autophosphorylation, dimerization, binding, and pathway assays in patient cells

    PMID:27426733 PMID:27426734

    Open questions at the time
    • How a single recurrent mutation alters multiple downstream pathways without affecting dimerization or TAB2 binding is unexplained
    • Tissue selectivity of skeletal phenotypes not addressed
  5. 2016 Medium

    Defined MAP3K7 as a required effector of BMP-induced adipogenesis acting via PPARγ transactivation with TAB1, connecting the kinase to metabolic differentiation and diet-induced obesity.

    Evidence Inhibitor/siRNA in preadipocytes, adipocyte-specific conditional KO mice, PPARγ transactivation and TAB1 co-activation assays

    PMID:27293199

    Open questions at the time
    • Whether TAK1 phosphorylates PPARγ directly or acts through co-activators is unclear
    • Single-lab finding
  6. 2016 Medium

    Identified MAP3K7 as the kinome hub rewiring MAPK networks during monocyte-to-macrophage differentiation and as the intracellular target of sorafenib, explaining keratinocyte toxicity in hand-foot skin reaction.

    Evidence Phosphoproteomics in THP-1 cells; transporter RNAi screen with in situ kinome profiling and in vivo rescue

    PMID:26677977 PMID:27066479

    Open questions at the time
    • Direct substrate map during differentiation not defined
    • On-target vs off-target contributions of sorafenib not fully separated
  7. 2017 Medium

    Demonstrated that constitutively active MAP3K7 directs cardiomyocyte differentiation toward the sinoatrial node lineage, implicating the kinase in cardiac conduction-cell specification.

    Evidence Transgenic ES-cell overexpression with electrophysiology and marker analysis

    PMID:29281682

    Open questions at the time
    • Downstream transcriptional effectors of SAN specification not identified
    • Requires loss-of-function confirmation
  8. 2018 Medium

    Showed MAP3K7 maintains renal mesangial homeostasis by balancing p38 and JNK output, where its loss elevates JNK and suppresses PDGFRβ, causing spontaneous kidney scarring.

    Evidence Foxd1-Cre conditional Map3k7 KO mice with p38/JNK and PDGFRβ readouts and JNK inhibition in isolated cells

    PMID:29667914

    Open questions at the time
    • Mechanism linking JNK to PDGFRβ repression not defined
    • Single-lab in vivo model
  9. 2019 Medium

    Expanded MAP3K7 roles into endoderm differentiation and HCC progression, activating p38/JNK/NLK to drive cardiogenic endoderm and engaging an mTOR axis to promote tumor growth.

    Evidence ES-cell overexpression with chimeric embryoid bodies and inhibitor studies; kinome siRNA screen with knockdown and xenografts in HCC

    PMID:31214512 PMID:31668971

    Open questions at the time
    • Whether MAP3K7 acts directly upstream of mTOR or indirectly is unresolved
    • NLK activation mechanism not characterized
  10. 2021 High

    Established multiple layers of MAP3K7 regulation and output: TRIM31-mediated K48 ubiquitination at Lys72 controls its degradation, iRhom2 binding promotes its phosphorylation in metabolic disease, and TAK1–IKKβ controls androgen receptor protein stability and HR-repair gene expression in prostate cancer.

    Evidence Reconstituted ubiquitination with site mutagenesis and KO/OE mouse models; reciprocal Co-IP and genetic models; conditional KO mice with AR ubiquitination and HR foci assays

    PMID:31300540 PMID:32592194 PMID:33846123 PMID:34158377 PMID:34584221

    Open questions at the time
    • How these distinct regulatory inputs are integrated on one kinase is unknown
    • Direct substrate phosphorylation events for AR and HR-gene control not fully mapped
  11. 2022 High

    Connected SF3B1-mutant mis-splicing to MAP3K7 depletion via NMD, defining an end-to-end mechanism whereby kinase loss deactivates p38, downregulates GATA1, and disrupts erythropoiesis in MDS.

    Evidence Splice/branchpoint analysis and NMD assays in isogenic and patient cells with knockdown/rescue and erythroid differentiation readouts

    PMID:33751071 PMID:34930825

    Open questions at the time
    • Why MAP3K7 is selectively vulnerable to SF3B1-driven mis-splicing is unclear
    • Direct GATA1 regulatory mechanism downstream of p38 not detailed
  12. 2024 Medium

    Refined the structural basis of CSCF pathogenicity by showing the Val50Ala variant disrupts ATP binding and kinase-domain structure to reduce autophosphorylation, with TGF-β partially restoring downstream signaling, distinguishing it from FMD2 variants.

    Evidence HEK293T overexpression with phosphorylation Western blots, 3D modeling, and TGF-β rescue

    PMID:42040894

    Open questions at the time
    • Endogenous patient-cell validation not performed
    • Mechanism of differential downstream pathway effects vs FMD2 unresolved
  13. 2025 Medium

    Proposed MAP3K7 as a cancer-intrinsic cytoprotective checkpoint and a regulator of genomic integrity: it integrates TNF/IFNγ to suppress RIPK1/Caspase-8 inflammatory death by stabilizing cFLIP, and phosphorylates EphA2-Ser897 to control RAD51 and prevent cGAS-STING activation.

    Evidence Kinome CRISPR screen, KO/inhibition, and syngeneic tumor models (preprint); proteomics, kinase assays, and GEMM (preprint)

    PMID:bio_10.1101_2025.05.09.652721 PMID:bio_10.1101_2025.10.08.681226

    Open questions at the time
    • Findings reside in preprints not yet peer-reviewed
    • Direct EphA2 and cFLIP phosphorylation/degradation steps require independent confirmation
  14. 2026 Medium

    Linked MAP3K7 loss to enhanced anti-tumor immunity, showing co-loss with CHD1 potentiates IFN-γ responses and sensitizes tumors to T-cell killing and checkpoint blockade.

    Evidence Genome-wide CRISPR screens in tumoroid–T cell co-cultures and syngeneic melanoma model

    PMID:41564866

    Open questions at the time
    • Mechanism by which MAP3K7 normally restrains IFN-γ transcriptional output not fully defined
    • Contribution of MAP3K7 loss independent of CHD1 not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how MAP3K7 integrates its many regulatory inputs (TAB adaptors, TRIM31 ubiquitination, iRhom2, transcript splicing) to select among its divergent downstream outputs across distinct tissues and disease contexts.
  • No unified model of context-dependent substrate selection
  • Direct phosphorylation targets in most contexts remain unmapped
  • Structural basis of differential signaling between disease variants undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 4 GO:0140657 ATP-dependent activity 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-73894 DNA Repair 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-5357801 Programmed Cell Death 1
Partners
BCL10CARMA1EPHA2IKBKBIRHOM2TAB1TAB2TRIM31
Complex memberships
TAK1-TAB1-TAB2 complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 Gain-of-function mutations in MAP3K7 (including the recurrent p.Pro485Leu near the coiled-coil domain and three kinase-domain missense mutations) cause frontometaphyseal dysplasia type 2. The recurrent mutation does not destabilize TAK1 or impair homodimerization or TAB2 binding, but increases TAK1 autophosphorylation and alters activity of multiple signaling pathways downstream of the TAK1 complex. Whole-exome sequencing, Sanger sequencing, autophosphorylation assays, homodimerization assays, TAB2 binding assays, downstream pathway activity assays in patient-derived cells American Journal of Human Genetics High 27426733
2016 Loss-of-function heterozygous MAP3K7 mutations cause cardiospondylocarpofacial syndrome by impairing MAPK-p38 signaling; expression of non-canonical TGF-β-driven target genes was impaired in fibroblasts from affected individuals, supporting loss of transcriptional control of the TGF-β–MAPK–p38 pathway. Whole-exome sequencing, reporter gene assays for MAPK-p38 signaling in patient fibroblasts American Journal of Human Genetics Medium 27426734
2020 The CSCF-associated MAP3K7 splice variant c.737-7A>G generates an in-frame insertion of 2 amino acids (p.Asn245_Gly246insValVal) in the kinase activation loop, which impairs TAK1 autophosphorylation, disrupts physical binding to TAB1 (shown by co-immunoprecipitation), impairs TGF-β-mediated α-SMA cytoskeleton assembly and cell migration, and causes defective autophagy in patient fibroblasts. RNA splice analysis, computational protein dynamics modeling, co-immunoprecipitation, autophosphorylation assays, α-SMA cytoskeleton and migration assays, autophagy assays in patient fibroblasts Biochimica et Biophysica Acta. Molecular Basis of Disease High 32105826
2021 TRIM31, an E3 ubiquitin ligase, interacts with MAP3K7 and catalyzes K48-linked polyubiquitination at lysine 72 of MAP3K7, leading to its proteasomal degradation and consequent negative regulation of TGF-β1-mediated Smad and MAPK/NF-κB signaling pathways in hypertensive renal disease. Co-immunoprecipitation, ubiquitination assays with K48-linkage specificity, site-directed mutagenesis (K72), proteasome inhibitor experiments, TRIM31 KO and AAV-overexpression mouse models, Western blotting for downstream pathway components Cell Death and Differentiation High 34584221
2022 SF3B1 mutations cause aberrant splicing of MAP3K7, generating a transcript with a premature termination codon targeted by nonsense-mediated decay, thereby reducing MAP3K7 protein. MAP3K7 is an upstream positive effector of p38 MAPK; its loss deactivates p38 MAPK, leading to premature down-regulation of GATA1, accelerated erythroid differentiation, erythroid hyperplasia, and apoptosis, explaining the anemia in SF3B1-mutated MDS. Isogenic SF3B1 WT vs. mutant cell lines, normal human CD34+ cells, MDS patient cells; splice analysis, cycloheximide NMD assay, MAP3K7 knockdown/rescue, p38 MAPK activity assays, GATA1 expression analysis, erythroid differentiation assays Proceedings of the National Academy of Sciences of the United States of America High 34930825
2021 MAP3K7 aberrant splicing induced by SF3B1 K700E mutation uses an aberrant 3′ splice site and alternative branchpoint sequence, and requires both a normal and an alternative upstream polypyrimidine tract; the aberrantly spliced transcript contains a premature termination codon targeted by NMD. SF3B1 K700E transfection in HEK293T cells, cycloheximide NMD assay, splice site and branchpoint mutational analysis Journal of Biochemistry Medium 33751071
2021 MAP3K7 activates IKKβ in response to TNFα, which phosphorylates AR protein, targeting it for TRCP1/2 E3 ligase-mediated polyubiquitination and proteasomal degradation; Map3k7 knockout in mouse prostate increased AR protein levels and activity, and AR protein levels were inversely correlated with MAP3K7 in patient specimens. Map3k7 conditional knockout mouse model, TNFα stimulation, AR ubiquitination assays, IKKβ phosphorylation assays, patient specimen correlation, prostate cancer cell lines Cancer Research High 34158377
2021 iRhom2 binds MAP3K7 and facilitates MAP3K7 phosphorylation in response to high-fat diet, activating the NF-κB cascade and promoting c-Jun N-terminal kinase/IRS1 signaling while disturbing AKT/GSK3β-associated insulin signaling; iRhom2/MAP3K7 axis is required for iRhom2-regulated liver steatosis. Co-immunoprecipitation of iRhom2 and MAP3K7, iRhom2 KO and OE mouse models (including myeloid-specific), bone marrow transplantation, phosphorylation assays, downstream pathway readouts Hepatology High 32592194
2012 TAK1 (MAP3K7) activation requires TAB1- or TAB2-dependent mechanisms; Tab1/Tab2 double deletion phenocopied Tak1 single deletion in hematopoietic stem cells, abolishing HSC reconstitution activity. TAK1 signaling maintains HSCs via two mechanisms: preventing TNF-dependent cell death (Tnfr1 deficiency partially rescued Tak1-deficient HSC reconstitution) and a TNF-independent long-term HSC maintenance pathway. Competitive transplantation assays, Tak1/Tab1/Tab2 conditional knockout mouse models, Tnfr1 double-knockout epistasis, LSK cell proliferation and death assays PloS ONE High 23226465
2013 In NK cells, a Fyn–ADAP complex exclusively regulates inflammatory cytokine production (not cytotoxicity) through a Carma1–Bcl-10–MAP3K7 signaling axis downstream of PI(3)K and PLC-γ2. Genetic knockouts/knockdowns of pathway components in NK cells, NK cell cytotoxicity assays, cytokine production assays, epistasis analysis Nature Immunology High 24036998
2016 TAK1 (MAP3K7) is required for BMP-induced adipocyte differentiation; TAK1 promotes PPARγ transcriptional activity synergistically with TAB1, and TAK1 ablation specifically in adipocytes reduced high-fat diet-induced weight gain and improved glucose tolerance. TAK1 inhibitor treatment, siRNA knockdown in C3H10T1/2 MSCs and 3T3-L1 preadipocytes, adipocyte-specific conditional knockout mice, PPARγ transactivation assay, co-activation assay with TAB1 Journal of Cellular Biochemistry Medium 27293199
2018 Genetic inactivation of Map3k7 in FOXD1-expressing mesangial/interstitial cells causes spontaneous postnatal kidney scarring; MAP3K7 loss skews MAPK signaling in mesangial cells (depressed p38, elevated JNK), and elevated JNK negatively regulates PDGFRβ expression, leading to loss of mesangial PDGFRβ. Foxd1-Cre conditional Map3k7 knockout mice, p38 and JNK phosphorylation assays, PDGFRβ expression analysis, isolated mesangial cell studies with JNK inhibition American Journal of Physiology. Renal Physiology Medium 29667914
2019 MAP3K7 promotes HCC cell proliferation, migration, and invasion through the MAP3K7–mTOR axis; MAP3K7 knockdown reduced mTOR phosphorylation and expression in HCC cells, and MAP3K7 expression was positively correlated with mTOR in patient tumors. Kinome siRNA library screen, pharmacological inhibition, stable MAP3K7 knockdown, spheroid culture, xenograft mouse model, mTOR phosphorylation Western blot, primary HCC cells Frontiers in Oncology Medium 31214512
2019 Loss of MAP3K7 in prostate cancer cells disrupts homologous recombination repair by reducing expression of ATM, ATR, BRCA2, RAD51, blocking BRCA1 phosphorylation, reducing RAD51 foci, and increasing γH2AX foci, sensitizing cells to CDK1/2 inhibition and DNA-damaging agents. MAP3K7/CHD1 knockdown in mouse and human prostate cells, CDK1/2 inhibitor (dinaciclib) treatment, HR gene expression analysis, RAD51 and γH2AX immunofluorescence foci assays, BRCA1 phosphorylation Western blot, PARP inhibitor co-treatment cytotoxicity Molecular Cancer Research Medium 31300540
2015 In multikinase inhibitor-induced hand-foot skin reaction, sorafenib enters keratinocytes via the OAT6 transporter (SLC22A20) and then inhibits MAP3K7 (TAK1) kinase activity, inducing keratinocyte cell death; in situ kinome profiling identified MAP3K7 as the intracellular sorafenib target. Transporter-directed RNAi screen in keratinocytes, in situ kinome profiling, MAP3K7 functional assays, in vivo keratinocyte injury model with OAT6 inhibitor rescue Cancer Research Medium 26677977
2016 MAP3K7 (TAK1) acts as the key signaling hub for bacterial killing, chemokine production, and monocyte-to-macrophage differentiation; kinomics and phosphoproteomics revealed that MAP3K7 is central to rewiring of MAPK signaling networks during differentiation. Kinomics and phosphoproteomics of THP-1 cells before/after macrophage differentiation, MAP3K7 functional inhibition with phenotypic readouts (bacterial killing, chemokine production, differentiation) Frontiers in Cell and Developmental Biology Medium 27066479
2012 Activin A stimulates murine and ovine Fshb transcription via SMAD proteins (SMAD3 and SMAD4), but NOT through TAK1 (MAP3K7) or p38 MAPK; Map3k7 siRNA failed to antagonize activin A-stimulated Fshb promoter activity, and activin A did not stimulate p38 phosphorylation in LβT2 gonadotrope-like cells. Map3k7 siRNA knockdown, TAK1 inhibitor (5Z-7-Oxozeaenol) dose-response, constitutively active ALK4 reporter assay, p38 phosphorylation Western blot, Smad3/Smad4 siRNA knockdown, luciferase promoter assays Cellular Signalling Medium 22549017
2017 Overexpression of constitutively active MAP3K7 in mouse ES-derived cardiomyocytes directs differentiation toward the sinoatrial node (SAN) lineage, producing cells with SAN markers, morphologies, and electrophysiological behaviors; Map3k7 is upregulated in the sinus venosus, the source of SAN progenitors. Transgenic ES cell overexpression of Map3k7, embryoid body differentiation, electrophysiology, molecular marker analysis PloS ONE Medium 29281682
2019 Map3k7 is required for endoderm differentiation; its overexpression in ES cells increases cardiogenic endoderm formation and visceral endoderm markers, enhancing cardiac differentiation of co-cultured wild-type cells. Downstream targets activated by Map3k7 include p38 MAPK, JNK, and NLK; inhibition of Map3k7 phosphorylation blocked these targets and impaired endoderm differentiation. Map3k7-overexpressing ES cell lines, chimeric embryoid bodies with MHCα::GFP reporter, 5Z-7-oxozeaenol inhibitor treatment, Western blot for JNK/p38/NLK, qRT-PCR for lineage markers Journal of Molecular and Cellular Cardiology Medium 31668971
2024 MAP3K7 Val50Ala variant (CSCF-causing) significantly reduces TAK1 autophosphorylation levels in HEK293T cells; the Val50 residue is critical for ATP binding and its substitution disrupts kinase domain structure. The variant differentially affects downstream signaling (p38, p65/NF-κB, JNK) compared to FMD2-causing variants; TGF-β stimulation partially restores altered phosphorylation. In vitro overexpression in HEK293T cells, Western blotting for TAK1 phosphorylation and downstream targets, protein 3D modeling, sequence conservation analysis, TGF-β stimulation rescue experiment Human Mutation Medium 42040894
2025 TAK1 (MAP3K7) acts as a cancer-intrinsic cytoprotective checkpoint by integrating TNF and IFNγ signals; TAK1 deficiency redirects combined TNF/IFNγ signaling to promote inflammatory cell death via RIPK1 and Caspase-8, amplifies IFNγ pathway output, and leads to proteasomal degradation of cFLIP, enhancing Complex II formation. TAK1 inhibition or loss attenuates tumor growth in immune-competent mice. Kinome-wide CRISPR/Cas9 sgRNA screen, TAK1 knockout and inhibition, TNF/IFNγ cytokine stimulation assays, RIPK1/Caspase-8 pathway analysis, cFLIP degradation assays, Complex II formation assays, syngeneic mouse tumor models, adoptive cell therapy bioRxivpreprint Medium bio_10.1101_2025.05.09.652721
2025 TAK1 (MAP3K7) phosphorylates EphA2 at Serine 897, which in turn phosphorylates RAD51 at Tyrosine 315; TAK1 inhibition induces DNA damage and cytoplasmic DNA leakage activating cGAS–STING, thereby promoting adaptive immune cell infiltration in pancreatic cancer. Proteomics, in vitro kinase/phosphorylation assays, TAK1 inhibitor (Takinib), MAP3K7 conditional genetic deletion in autochthonous GEMM (p48-Cre;TP53flox/flox;LSL-KRASG12D), scRNA-seq, flow cytometry, mIHC, cGAS-STING pathway assays bioRxivpreprint Medium bio_10.1101_2025.10.08.681226
2021 MAP3K7 loss drives increased androgen receptor (AR) target gene expression and increased AR-v7 expression in prostate cancer; CHD1 loss mainly expands the AR cistrome, while MAP3K7 loss primarily increases AR target gene transcription. Co-suppression of MAP3K7 and CHD1 confers resistance to enzalutamide. Engineered prostate cancer cell lines with MAP3K7/CHD1 co-suppression, AR ChIP-seq/cistrome analysis, AR target gene expression profiling, enzalutamide resistance assays, clinical cohort AR-v7 expression Molecular Cancer Research Medium 33846123
2026 Loss of MAP3K7 (and CHD1) potentiates the transcriptional response to IFN-γ in cancer cells, sensitizing them to tumor-reactive T cell killing; MAP3K7/CHD1 co-loss increases susceptibility to immune checkpoint blockade in syngeneic mouse models, associated with elevated intra-tumoral CD8+ T cell numbers and activation. Whole-genome CRISPR-Cas9 KO screens in tumoroid-T cell co-cultures and isogenic IFN-signaling-deficient models, syngeneic mouse melanoma model with Chd1/Map3k7 deficiency, flow cytometry for T cell infiltration and activation Cell Reports Medicine Medium 41564866
2024 MAP3K7 phosphorylation is increased in both muscle hypertrophy (Texel sheep) and cancer-induced cachexia; in C2C12 cells, blockade of TAK1 phosphorylation reduces downstream phosphorylation of p38, JNK, and HSP27, and acutely promotes muscle fiber hypertrophy, but continuous blockade leads to muscle fiber failure. Multiplex kinase array of ES cells with/without TAK1 stimulation, phosphoprotein analysis in Texel sheep and cachexia mouse models, C2C12 myofiber differentiation with TAK1 phosphorylation blockade Biology Open Low 39211992

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Genomic deletion of MAP3K7 at 6q12-22 is associated with early PSA recurrence in prostate cancer and absence of TMPRSS2:ERG fusions. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 125 23370768
2015 Coordinate loss of MAP3K7 and CHD1 promotes aggressive prostate cancer. Cancer research 76 25770290
2013 Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells. Nature immunology 76 24036998
2015 MiR-377 targets E2F3 and alters the NF-kB signaling pathway through MAP3K7 in malignant melanoma. Molecular cancer 68 25889255
2016 Induction of Macrophage Function in Human THP-1 Cells Is Associated with Rewiring of MAPK Signaling and Activation of MAP3K7 (TAK1) Protein Kinase. Frontiers in cell and developmental biology 60 27066479
2016 Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia. American journal of human genetics 59 27426733
2007 Deletion of a small consensus region at 6q15, including the MAP3K7 gene, is significantly associated with high-grade prostate cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 58 17785553
2022 SF3B1 mutant-induced missplicing of MAP3K7 causes anemia in myelodysplastic syndromes. Proceedings of the National Academy of Sciences of the United States of America 57 34930825
2021 The E3 ubiquitin ligase TRIM31 plays a critical role in hypertensive nephropathy by promoting proteasomal degradation of MAP3K7 in the TGF-β1 signaling pathway. Cell death and differentiation 57 34584221
2017 TAK-ing aim at chemoresistance: The emerging role of MAP3K7 as a target for cancer therapy. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 54 29145973
2015 Multikinase Inhibitors Induce Cutaneous Toxicity through OAT6-Mediated Uptake and MAP3K7-Driven Cell Death. Cancer research 42 26677977
2020 Long non-coding RNA CCDC144NL-AS1 sponges miR-143-3p and regulates MAP3K7 by acting as a competing endogenous RNA in gastric cancer. Cell death & disease 41 32647147
2016 Heterozygous Mutations in MAP3K7, Encoding TGF-β-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome. American journal of human genetics 36 27426734
2017 MicroRNA-143 inhibits cell growth by targeting ERK5 and MAP3K7 in breast cancer. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 32 28746466
2019 The MAP3K7-mTOR Axis Promotes the Proliferation and Malignancy of Hepatocellular Carcinoma Cells. Frontiers in oncology 26 31214512
2009 Combined inhibition of PAK7, MAP3K7 and CK2alpha kinases inhibits the growth of MiaPaCa2 pancreatic cancer cell xenografts. Cancer gene therapy 24 19363471
2020 PCAT-1 promotes cell growth by sponging miR-129 via MAP3K7/NF-κB pathway in multiple myeloma. Journal of cellular and molecular medicine 22 32048803
2021 iRhom2 Promotes Hepatic Steatosis by Activating MAP3K7-Dependent Pathway. Hepatology (Baltimore, Md.) 21 32592194
2018 Overexpression of miR-155-5p Inhibits the Proliferation and Migration of IL-13-Induced Human Bronchial Smooth Muscle Cells by Suppressing TGF-β-Activated Kinase 1/MAP3K7-Binding Protein 2. Allergy, asthma & immunology research 21 29676073
2021 MAP3K7 Loss Drives Enhanced Androgen Signaling and Independently Confers Risk of Recurrence in Prostate Cancer with Joint Loss of CHD1. Molecular cancer research : MCR 19 33846123
2019 Loss of MAP3K7 Sensitizes Prostate Cancer Cells to CDK1/2 Inhibition and DNA Damage by Disrupting Homologous Recombination. Molecular cancer research : MCR 19 31300540
2018 A novel MAP3K7 splice mutation causes cardiospondylocarpofacial syndrome with features of hereditary connective tissue disorder. European journal of human genetics : EJHG 18 29467388
2021 MAP3K7-IKK Inflammatory Signaling Modulates AR Protein Degradation and Prostate Cancer Progression. Cancer research 17 34158377
2012 Activin A induction of murine and ovine follicle-stimulating hormone β transcription is SMAD-dependent and TAK1 (MAP3K7)/p38 MAPK-independent in gonadotrope-like cells. Cellular signalling 16 22549017
2016 BMP-TAK1 (MAP3K7) Induces Adipocyte Differentiation Through PPARγ Signaling. Journal of cellular biochemistry 15 27293199
2018 MAP3K7 is recurrently deleted in pediatric T-lymphoblastic leukemia and affects cell proliferation independently of NF-κB. BMC cancer 14 29914415
2022 The MAP3K7 gene: Further delineation of clinical characteristics and genotype/phenotype correlations. Human mutation 13 35730652
2019 Prostatic adenocarcinoma CNS parenchymal and dural metastases: alterations in ERG, CHD1 and MAP3K7 expression. Journal of neuro-oncology 13 30656528
2012 TAK1 (MAP3K7) signaling regulates hematopoietic stem cells through TNF-dependent and -independent mechanisms. PloS one 13 23226465
2020 MAP3K7 and CHD1 Are Novel Mediators of Resistance to Oncolytic Vesicular Stomatitis Virus in Prostate Cancer Cells. Molecular therapy oncolytics 12 32529027
2020 TWIST1-MicroRNA-10a-MAP3K7 Axis Ameliorates Synovitis of Osteoarthritis in Fibroblast-like Synoviocytes. Molecular therapy. Nucleic acids 12 33294296
2020 A novel variant in MAP3K7 associated with an expanded cardiospondylocarpofacial syndrome phenotype. Cold Spring Harbor molecular case studies 11 32299812
2012 MAP3K7 and GSTZ1 are associated with human longevity: a two-stage case-control study using a multilocus genotyping. Age (Dordrecht, Netherlands) 10 22576335
2020 Insights into the molecular pathogenesis of cardiospondylocarpofacial syndrome: MAP3K7 c.737-7A > G variant alters the TGFβ-mediated α-SMA cytoskeleton assembly and autophagy. Biochimica et biophysica acta. Molecular basis of disease 9 32105826
2018 Inactivation of MAP3K7 in FOXD1-expressing cells results in loss of mesangial PDGFRΒ and juvenile kidney scarring. American journal of physiology. Renal physiology 9 29667914
2022 MAP3K7 is an innate immune regulatory gene with increased expression in human and murine kidney intercalated cells following uropathogenic Escherichia coli exposure. Journal of cellular biochemistry 8 35959632
2017 Overexpression of Map3k7 activates sinoatrial node-like differentiation in mouse ES-derived cardiomyocytes. PloS one 8 29281682
2018 Expansion of the clinical spectrum of frontometaphyseal dysplasia 2 caused by the recurrent mutation p.Pro485Leu in MAP3K7. European journal of medical genetics 6 29660408
2021 Characterization of the aberrant splicing of MAP3K7 induced by cancer-associated SF3B1 mutation. Journal of biochemistry 5 33751071
2021 Expanding the phenotypic spectrum of cardiospondylocarpofacial syndrome: From a detailed clinical and radiological observation of a boy with a novel missense variant in MAP3K7. American journal of medical genetics. Part A 5 34558790
2019 TAK1/Map3k7 enhances differentiation of cardiogenic endoderm from mouse embryonic stem cells. Journal of molecular and cellular cardiology 5 31668971
2019 Evidence for a Role of TGF-β-Activated Kinase 1 and MAP3K7 Binding Protein 3 in Peanut-Specific T-Cell Responses. International archives of allergy and immunology 3 30893695
2017 Overexpression of constitutively active MAP3K7 in ameloblasts causes enamel defects of mouse teeth. Archives of oral biology 3 29024853
2024 A severe case of cardiospondylocarpofacial syndrome with a novel MAP3K7 variant. Human genome variation 2 38383446
2024 The N6-methyladenosine pattern of MAP3K7 mediates the effects of sevoflurane on macrophage M2 polarization and cervical cancer migration and invasion. Central-European journal of immunology 2 39944262
2022 A novel MAP3K7 mutation in a child with cardiospondylocarpofacial syndrome and orofacial clefting. Clinical genetics 2 36320120
2021 High Expression of LINC01268 is Positively Associated with Hepatocellular Carcinoma Progression via Regulating MAP3K7. OncoTargets and therapy 2 33727826
2020 Differential expression of MAP3K7 and TROPONIN C proteins and related perturbations in renal amyloidosis. Expert review of proteomics 2 33023362
2025 Silencing Map3k7 suppresses pyroptosis to alleviate bronchopulmonary dysplasia through inhibiting the TGF-β1/Smad3 pathway. General physiology and biophysics 1 39815896
2023 Early and severe tricuspid valve dysplasia in a fetus with cardiospondylocarpofacial syndrome due to a variant c.616T>G p.(Tyr206Asp) in MAP3K7. Prenatal diagnosis 1 37160697
2026 CRISPR screens in the context of immune selection identify CHD1 and MAP3K7 as mediators of cancer immunotherapy resistance. Cell reports. Medicine 0 41564866
2026 Exosomal miR-10b derived from protocatechuic acid-treated efferocytic macrophages inhibits endothelial inflammation by targeting MAP3K7/β-TrCP/NF-κB signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41678912
2026 Genetic variants and serum biomarkers of CXCL8, MAP3K7, LTA/TNF, EXOC3L1, PROCR, and TRAF2 in Age-Related macular degeneration: associations with disease risk and therapeutic response. Scientific reports 0 41844873
2026 A Novel MAP3K7 Variant Causing Loss of Function Identified in a Family With Cardiospondylocarpofacial Syndrome: Functional Validation and Molecular Insights. Human mutation 0 42040894
2026 Divergent RNA structures support accurate splicing of the SF3B1-sensitive MAP3K7 intron. bioRxiv : the preprint server for biology 0 42239186
2025 Exosomal tpi-miR-10a-5p from T. pisiformis cysticerci regulates the expression of inflammatory factors in rabbits by targeting MAP3K7. Veterinary parasitology 0 40628081
2025 Neonatal dilated cardiomyopathy and cardiospondylocarpofacial syndrome linked to a novel MAP3K7 gene mutation. Annals of pediatric cardiology 0 40814318
2024 Analysis of potential TAK1/Map3k7 phosphorylation targets in hypertrophy and cachexia models of skeletal muscle. Biology open 0 39211992
2024 Unraveling a Genetic Puzzle: Could MAP3K7 Be a Candidate Gene for RASopathies? Journal of clinical research in pediatric endocrinology 0 39415662
2022 Generation of the induced pluripotent stem cell line UNIBSi017-A from an individual with cardiospondylocarpofacial syndrome and the MAP3K7 c.737-7A > G variant. Stem cell research 0 35700636

Missed literature

Know a paper Affinage missed for MAP3K7? Flag it for the maintainers and the community.

No submissions yet.