Affinage

SMAD3

SMAD family member 3 · UniProt P84022

Length
425 aa
Mass
48.1 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMAD3 is the central signal-transducing transcription factor of the TGF-β/activin pathway, coupling receptor activation at the membrane to gene-regulatory programs that govern fibrosis, immune regulation, cancer progression, and tissue development (PMID:9311995, PMID:28262747, PMID:34791825). Upon TGF-β stimulation, SMAD3 is recruited to and phosphorylated by the activated TβR-I/II receptor complex, forms heteromeric complexes with SMAD4 (and SMAD2), translocates to the nucleus, and synergistically activates target promoters such as PAI-1 (PMID:9311995); SARA recognizes monomeric SMAD3 while phosphorylation-driven trimerization simultaneously releases SARA and exposes SMAD3 to Ski-mediated negative feedback (PMID:12154125). Activation is gated by a dense layer of post-translational modifications: C-terminal SSXS phosphorylation is essential while linker-region phosphorylation acts as a brake (PMID:23022526), ERK phosphorylation at Ser203/Ser207/Thr178 and GSK3-β phosphorylation at Thr66 (driving Axin-dependent proteasomal degradation) restrain activity (PMID:16156666, PMID:18172167), hypoxic PP2A dephosphorylates SMAD3 specifically (PMID:19951945), EZH2 methylation at K53/K333 promotes the SARA interaction and receptor-mediated phosphorylation (PMID:35085106), p300/CBP acetylation at Lys19 and KAT5 acetylation at K333 enhance DNA binding and sustain activity (opposed by SIRT2 deacetylation) (PMID:17074756, PMID:29520103, PMID:37777567), and mono-ubiquitination and Cys64 sulfenylation each inhibit DNA binding, the former reversed by USP7 to enable SMAD3 autoregulation (PMID:34580281, PMID:33647858). In the nucleus, distinct hydrophobic patches on the SMAD3 MH2 domain confer cofactor selectivity — a crystal structure of the MH2–FOXH1 complex established how SMAD3 versus SMAD2 recruit different partners (PMID:29588413) — allowing SMAD3 to engage a wide range of context-specific cofactors including FoxL2, Scleraxis/Mohawk, ATOH8, STAT3, the androgen receptor, BRCA1/BRCA2, and WWOX to activate or repress transcription (PMID:19106105, PMID:23653374, PMID:36626550, PMID:11280774, PMID:12165866, PMID:15735739, PMID:24330518). Through these interactions SMAD3 binds defined promoter and enhancer elements to control collagen, PAI-1, miR-192, miR-200, the NK-cell factor E4BP4/NFIL3, TFEB, and AR, thereby driving renal and tendon fibrosis, macrophage-to-myofibroblast transition, muscle atrophy, NK-cell immunosuppression, and EMT/stemness programs (PMID:20488955, PMID:22020340, PMID:28262747, PMID:33043774, PMID:34791825, PMID:24002653, PMID:28288136). SMAD3 function is consistently distinguished from SMAD2, which acts as a counterbalancing or opposing regulator across renal, immune, and developmental contexts (PMID:20595680, PMID:26141582).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1997 High

    Established SMAD3 as a direct receptor-activated effector of TGF-β, answering how an extracellular cytokine signal reaches the nucleus to control transcription.

    Evidence Co-IP, phosphorylation assays, nuclear translocation imaging, and PAI-1 reporter assays across COS, Mv1Lu, and HSC4 cells

    PMID:9311995

    Open questions at the time
    • Did not resolve the structural basis of receptor recognition
    • Stoichiometry of the SMAD2/3/4 complex left undefined
  2. 2001 High

    Showed SMAD3 functions not only as an activator but as a direct transcriptional repressor, here of androgen-receptor-mediated transcription, expanding its regulatory repertoire.

    Evidence GST pulldown, Co-IP, and reporter assays mapping the AR activation domain to the SMAD3 MH2 domain

    PMID:11280774

    Open questions at the time
    • Mechanism of repression at native chromatin not defined
    • Relationship to TGF-β stimulation unclear
  3. 2002 High

    Defined the allosteric logic linking phosphorylation to signaling state: monomeric SMAD3 binds SARA, trimeric SMAD3 binds Ski, so trimerization both activates and sets up negative feedback.

    Evidence Structural modeling with biochemical binding assays distinguishing monomeric vs. trimeric SMAD3

    PMID:12154125

    Open questions at the time
    • Based on modeling rather than experimental structures of full complexes
    • Kinetics of the monomer-to-trimer transition not measured
  4. 2002 Medium

    Linked SMAD3 to DNA-damage-response machinery by identifying BRCA2 as a bidirectional transcriptional partner.

    Evidence GST pulldown, endogenous Co-IP after TGF-β1, and luciferase reporter assays with domain mapping

    PMID:12165866

    Open questions at the time
    • Single lab
    • Functional consequence at endogenous target genes not established
  5. 2005 High

    Demonstrated that SMAD3 integrates RTK input, with ERK phosphorylating the linker to inhibit SMAD3 transcriptional output — a crosstalk node between growth-factor and TGF-β signaling.

    Evidence Phosphopeptide mapping, in vitro ERK2 kinase assay, mutagenesis of Ser203/Ser207/Thr178, reporter assay

    PMID:16156666

    Open questions at the time
    • In vivo relevance of each site not dissected
    • Mechanism by which linker phosphorylation reduces activity unresolved
  6. 2005 Medium

    Connected SMAD3 to DNA double-strand-break repair, showing TGF-β/SMAD3 antagonizes BRCA1-dependent repair.

    Evidence GST pulldown, Co-IP, confocal co-localization, comet and colony-survival assays, BRCA1 foci analysis

    PMID:15735739

    Open questions at the time
    • Single lab
    • Direct chromatin mechanism of repair interference not defined
  7. 2006 High

    Identified SMAD3-specific degradation control, with GSK3-β phosphorylating Thr66 in unstimulated cells to trigger Axin-scaffolded ubiquitin-proteasome turnover.

    Evidence Co-IP, proteasome inhibitor assays, in vitro phosphorylation, Thr66 mutagenesis, reporter assay

    PMID:18172167

    Open questions at the time
    • E3 ligase responsible not identified
    • Quantitative contribution to basal SMAD3 pool unclear
  8. 2006 High

    Established acetylation as a positive activating mark, with p300/CBP acetylating Lys19 to expose the MH1 DNA-binding domain.

    Evidence In vitro acetylation assay, Lys19 mutagenesis, acetyl-Lys19 antibody, DNA-binding and ChIP assays

    PMID:17074756

    Open questions at the time
    • Deacetylase counteracting Lys19 not identified here
    • Interplay with phosphorylation timing not resolved
  9. 2008 High

    Revealed cofactor-directed promoter selectivity, with FoxL2 recruiting SMAD3 specifically (not SMAD2/4) to the follistatin SBE1 enhancer.

    Evidence Co-IP, ChIP, luciferase reporter, shRNA knockdown, domain mapping requiring the forkhead domain

    PMID:19106105

    Open questions at the time
    • Structural basis of the MH2-forkhead interface not defined
    • Generality to other forkhead partners untested here
  10. 2009 High

    Showed SMAD3 signaling is tuned by environmental oxygen, with hypoxia-recruited PP2A specifically dephosphorylating SMAD3 to dampen nuclear accumulation.

    Evidence Co-IP, PP2A activity assay, nuclear translocation and gene-expression analysis, pharmacological PP2A inhibition; PR65 scaffold requirement

    PMID:19951945

    Open questions at the time
    • How hypoxia targets PP2A to SMAD3 specifically not defined
    • Phospho-sites dephosphorylated not mapped
  11. 2010 High

    Defined SMAD2 as a counterbalancing regulator of SMAD3 and identified miR-192 as a direct SMAD3 target driving fibrotic collagen output.

    Evidence Conditional Smad2 knockout, ChIP on COL1A2 and miR-192 promoters, phosphorylation and reporter assays, miRNA functional assays

    PMID:20488955 PMID:20595680

    Open questions at the time
    • Mechanism by which SMAD2 limits SMAD3 phosphorylation not fully resolved
    • Direct vs. indirect promoter occupancy at some loci inferred
  12. 2011 Medium

    Uncovered positive-feedback partners (TRB3) that stabilize phospho-SMAD3 and identified miR-200 as a TGF-β-independent SMAD3 target controlling EMT regulators.

    Evidence Co-IP and domain mapping, Smurf2 degradation assay, localization imaging; SBE-mutagenesis luciferase reporter and SMAD3 manipulation for miR-200

    PMID:21896644 PMID:22020340

    Open questions at the time
    • Single labs
    • ChIP occupancy at miR-200 promoter inferred rather than directly shown
  13. 2012 Medium

    Distinguished the functional roles of C-terminal versus linker phosphorylation, showing the SSXS tail is essential for activation while linker phosphorylation acts as a brake on EMT.

    Evidence EPSM and 3S-A SMAD3 mutants reconstituted into Smad3-deficient renal cells with EMT marker readouts

    PMID:23022526

    Open questions at the time
    • Kinases acting at each linker site in this context not assigned
    • Single lab
  14. 2013 Medium

    Extended SMAD3's reach into tendon, muscle, and a cytoplasmic myogenesis/fibrogenesis switch, defining tissue-specific cofactors and signaling crosstalk.

    Evidence Co-IP with Scleraxis/Mohawk and Smad3 KO histology; in vivo muscle transfection with atrogin-1/PGC1α readouts and miR-29/PTEN axis; p-Akt/SMAD3 Co-IP with IGF-I/TGF-β1 switching

    PMID:23653374 PMID:23736539 PMID:24002653

    Open questions at the time
    • Single labs per tissue
    • Direct vs. indirect transcriptional targets in atrophy not all mapped
  15. 2013 Medium

    Identified WWOX as a negative regulator that sequesters SMAD3 in the cytoplasm and reduces its promoter occupancy.

    Evidence Co-IP, GST pulldown, ChIP at ANGPTL4/SERPINE1, reporter assay, confocal localization, shRNA

    PMID:24330518

    Open questions at the time
    • Single lab
    • Whether sequestration is direct or via altered phosphorylation unclear
  16. 2015 Medium

    Established opposing SMAD2/SMAD3 control of immune programs, with SMAD3 required for TGF-β autoinduction in dendritic cells and engaging a STAT3 interaction that inhibits SMAD3 DNA binding.

    Evidence Smad2/Smad3-deficient dendritic cells with colitis model; reciprocal Co-IP, SMAD3-SMAD4 complex and DNA-binding assays with STAT3 domain mapping

    PMID:26141582 PMID:26616859

    Open questions at the time
    • Single labs
    • Context-dependence of STAT3 inhibition vs. cooperation not reconciled here
  17. 2015 Medium

    Identified PCDH1 as an endogenous brake on SMAD3 transcriptional activity in airway epithelium.

    Evidence Yeast two-hybrid, endogenous Co-IP, reporter and siRNA/overexpression functional assays with target qPCR

    PMID:26209277

    Open questions at the time
    • Single lab
    • Subcellular mechanism of inhibition not defined
  18. 2017 High

    Defined SMAD3-specific roles in immune and cancer-stemness programs: direct repression of E4BP4/NFIL3 to suppress NK-cell development, and a cooperative STAT3-SMAD3 axis driving EMP/stemness.

    Evidence Smad3 KO bone marrow with NK differentiation, E4BP4 ChIP/reporter, SIS3 inhibitor, tumor models; SMAD-specific ablation with nuclear fractionation and DNA-binding/phenotypic assays for OSM/STAT3

    PMID:28262747 PMID:28288136

    Open questions at the time
    • How STAT3 here promotes vs. elsewhere inhibits SMAD3 DNA binding not reconciled
    • Direct SMAD3 targets in stemness program not fully enumerated
  19. 2018 High

    Provided the structural explanation for cofactor selectivity, showing the SMAD3 MH2 domain uses distinct hydrophobic patches to recruit different partners (FOXH1 vs. SKI).

    Evidence X-ray crystal structures of SMAD3-FOXH1 and SMAD2-SKI complexes

    PMID:29588413

    Open questions at the time
    • Structures of additional cofactor complexes not solved
    • Affinity hierarchy among competing cofactors not measured
  20. 2018 Medium

    Added acetylation-based amplification, with TRIB3-recruited KAT5 acetylating K333 to sustain SMAD3 activity in a feedback loop druggable by metformin.

    Evidence Co-IP, in vitro acetylation, K333 mutagenesis, reporter assay, metformin treatment in vitro and in vivo

    PMID:29520103

    Open questions at the time
    • Single lab
    • Interplay between K333 acetylation and K333 methylation not resolved
  21. 2019 High

    Showed phagocytosis directly activates macrophage SMAD3 independent of TGF-β release, driving anti-inflammatory transition and adaptive cardiac remodeling.

    Evidence Myeloid-specific Smad3 conditional KO, myocardial infarction model, phagocytosis and cytokine assays, Mfge8 rescue

    PMID:31092129

    Open questions at the time
    • Receptor coupling phagocytosis to SMAD3 phosphorylation not identified
    • Direct vs. indirect control of Mfge8 not shown
  22. 2020 Medium

    Linked SMAD3 to autophagy and lysosomal biogenesis by direct repression of TFEB, explaining lysosome depletion in diabetic nephropathy.

    Evidence ChIP at the TFEB 3'-UTR, SMAD3 deletion/SIS3 inhibition, TFEB silencing rescue, lysosome/autophagy flux assays

    PMID:33043774

    Open questions at the time
    • Single lab
    • Mechanism of 3'-UTR-targeted transcriptional repression atypical and not fully explained
  23. 2021 High

    Established multiple new layers of SMAD3 regulation and output: USP7-mediated de-monoubiquitination enabling DNA binding and autoregulation, Cys64 sulfenylation as a redox off-switch, macrophage-to-myofibroblast transition generating CAFs, and a SMAD3/YAP role in neural tube morphogenesis.

    Evidence USP7 CRISPR KO with ChIP-seq/RNA-seq and ubiquitination assays; chemoproteomics with Cys64 mutagenesis in hypertension model; SMAD3 ChIP-seq with macrophage-specific KO and SIS3 in lung carcinoma; chick-embryo SMAD3 loss-of-function with live imaging

    PMID:33647858 PMID:33878300 PMID:34580281 PMID:34791825

    Open questions at the time
    • E3 ligase depositing the mono-ubiquitin not identified
    • Enzymatic source of Cys64 sulfenylation in vivo not defined
  24. 2022 Medium

    Defined methylation-driven activation and its acetyl/deacetyl counterbalance, plus SMAD3-specific chromatin output: EZH2 K53/K333 methylation promotes SARA binding and receptor phosphorylation, SIRT2 deacetylates K341/K378 to dampen activity, and SMAD3 drives SOX2 via H3K4me3.

    Evidence In vitro methylation/deacetylation reconstitution, site mutagenesis, SARA Co-IP, conditional KO mice, ChIP for histone marks, breast and ovarian cancer models

    PMID:35085106 PMID:35905726 PMID:37777567

    Open questions at the time
    • Combinatorial logic among competing modifications at shared residues (e.g., K333) not resolved
    • Some findings single-lab
  25. 2023 High

    Established genome-wide SMAD3 control of the androgen receptor and a SMAD3-ATOH8 senescence program, expanding SMAD3's transcriptional reach in cancer.

    Evidence SMAD3 and AR ChIP-seq with CRISPRi validation, RNA-seq, AR rescue, PROTAC inhibitor; ATOH8-SMAD3 Co-IP, SMAD-specific knockdown, ATOH8 deletion tumor model, SMAD3 inhibitor

    PMID:36626550 PMID:36727462

    Open questions at the time
    • How SMAD3 selects activating vs. repressive programs genome-wide not fully defined
    • Cofactor partition between AR co-occupancy and senescence loci unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dozens of competing post-translational modifications (often on shared residues such as K333) and the many context-specific cofactors are integrated to determine whether SMAD3 activates or represses a given locus remains unresolved.
  • No unified model reconciling competing modifications at shared lysines
  • Quantitative cofactor competition at the MH2 hydrophobic patches not mapped genome-wide
  • Determinants of activator vs. repressor mode at individual targets undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 4 GO:0060089 molecular transducer activity 2
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2
Partners
ARBRCA1FOXH1SARASMAD2SMAD4STAT3TRIB3
Complex memberships
SMAD3-SMAD2-SMAD4 receptor-activated complexSMAD3-SMAD4 complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 SMAD3 (and SMAD2) interact with the kinase-deficient TGF-β type I receptor (TβR-I) after it is phosphorylated by TβR-II kinase; TGF-β1 induces phosphorylation of SMAD3; upon TβR activation, SMAD3 forms heteromeric complexes with SMAD2 and SMAD4; these complexes translocate to the nucleus and synergistically activate TGF-β-inducible transcription (PAI-1 promoter). Dominant-negative SMAD3 inhibited the synergistic transcriptional response. Co-immunoprecipitation in COS cells, phosphorylation assays in Mv1Lu and HSC4 cells, nuclear translocation imaging, transcriptional reporter assay The EMBO journal High 9311995
2002 SARA (Smad Anchor for Receptor Activation) specifically recognizes monomeric SMAD3, while the transcriptional co-repressor Ski specifically recognizes trimeric SMAD3. Phosphorylation-induced trimerization of SMAD3 simultaneously drives dissociation from SARA (activating TGF-β signal) and sets up Ski-mediated negative feedback. Structural models of SMAD3/SARA/receptor kinase and SMAD3/Ski complexes were generated. Structural modeling, biochemical binding assays distinguishing monomeric vs. trimeric SMAD3, in vitro reconstitution Genes & development High 12154125
2005 ERK MAP kinase phosphorylates SMAD3 at Ser207, Ser203, and Thr178 in the linker region upon EGF treatment. Phosphorylation peaks at 15–30 min, is blocked by MEK1 inhibitors, and is recapitulated by recombinant ERK2 in vitro. Mutation of these ERK sites increases SMAD3 transcriptional activity on a Smad target gene, indicating ERK phosphorylation inhibits SMAD3 activity. Phosphopeptide mapping, in vitro kinase assay with recombinant ERK2, site-directed mutagenesis, transcriptional reporter assay Biochemistry High 16156666
2006 Non-activated SMAD3 (but not SMAD2) undergoes proteasome-dependent degradation mediated by scaffolding protein Axin and its associated kinase GSK3-β. SMAD3 physically interacts with Axin and GSK3-β only in the absence of TGF-β. GSK3-β phosphorylates SMAD3 at Thr66, triggering SMAD3 ubiquitination and degradation. Thr66 mutants show altered protein stability and transcriptional activity. Co-immunoprecipitation, proteasome inhibitor assays, in vitro phosphorylation, site-directed mutagenesis of Thr66, transcriptional reporter assay Genes & development High 18172167
2006 SMAD3 DNA binding activity is enhanced by acetylation of Lys19 in the MH1 domain, mediated by coactivators p300 and CBP in a TGF-β-dependent manner. Acetylation of Lys19 induces a conformational change making the MH1 DNA-binding domain accessible. Acetyl-Lys19-specific antibodies confirmed endogenous SMAD3 acetylation in response to TGF-β. In vitro acetylation assay with p300/CBP, site-directed mutagenesis, acetyl-Lys19 antibody, DNA-binding assay, ChIP on target promoters The Journal of biological chemistry High 17074756
2009 Under hypoxic conditions, protein phosphatase 2A (PP2A) specifically dephosphorylates SMAD3 (but not SMAD2). PP2A physically interacts with SMAD3 only under hypoxia, and Smad3-associated PP2A activity is detectable under these conditions. The scaffold subunit PR65 is required for this hypoxic dephosphorylation. Hypoxia attenuates nuclear accumulation of TGF-β-induced SMAD3 and SMAD3-activated gene expression, which is reversed by chemical PP2A inhibition. Co-immunoprecipitation, PP2A activity assay, nuclear translocation assay, gene expression analysis, pharmacological PP2A inhibition The Journal of biological chemistry High 19951945
2001 SMAD3 specifically represses androgen receptor (AR)-mediated transcription on two natural androgen-responsive promoters. A direct protein-protein interaction between AR and SMAD3 was identified in vitro and in vivo; the transcription activation domain of AR binds the MH2 domain of SMAD3, and the repression of AR is mediated solely through the MH2 domain of SMAD3. Transient transfection reporter assays, GST pulldown (in vitro binding), co-immunoprecipitation (in vivo), domain-mapping mutagenesis Cancer research High 11280774
2002 BRCA2 forms a complex with SMAD3 in vitro and in vivo; both MH1 and MH2 domains of SMAD3 contribute to the interaction. TGF-β1 stimulates interaction of endogenous SMAD3 and BRCA2 in non-transfected cells. BRCA2 co-activates SMAD3-dependent transcriptional activation of PAI-1 and a luciferase reporter, and SMAD3 increases BRCA2 transcriptional activity. GST pulldown, co-immunoprecipitation of endogenous proteins, luciferase reporter assay, domain mapping Oncogene Medium 12165866
2005 SMAD3 (via its MH1 domain) forms a complex with BRCA1 in vitro and in vivo, and they co-localize in nuclear complexes. TGF-β1/SMAD3 counteracts BRCA1-dependent repair of DNA double-strand breaks, as measured by BRCA1 nuclear foci formation, single-cell gel electrophoresis, and cell survival assays. GST pulldown, co-immunoprecipitation, confocal co-localization, comet assay, colony survival assay, BRCA1 nuclear foci analysis Oncogene Medium 15735739
2008 FoxL2 directly associates with SMAD3 (but not SMAD2 or SMAD4) through its MH2 domain, and this interaction requires an intact forkhead domain in FoxL2. FoxL2 and SMAD3 are both recruited to the intronic Smad-binding element (SBE1) of the follistatin gene enhancer (confirmed by ChIP) and cooperate to drive activin/SMAD3-mediated follistatin transcription. shRNA knockdown of FoxL2 impairs SBE1-mediated transcription. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), luciferase reporter assay, shRNA knockdown, domain-mapping mutagenesis The Journal of biological chemistry High 19106105
2010 SMAD3 directly binds to the miR-192 promoter and mediates TGF-β1-induced miR-192 expression specifically (not SMAD2). miR-192 in turn promotes collagen matrix expression downstream of TGF-β/SMAD3 signaling in renal fibrosis. Smad3-selective knockdown/overexpression, promoter binding assay (ChIP), miR-192 mimic/inhibitor functional assays, collagen matrix assays Journal of the American Society of Nephrology : JASN Medium 20488955
2010 Smad2 deletion enhances TGF-β/SMAD3 signaling, increasing SMAD3 phosphorylation, nuclear translocation, promoter activity, and binding of SMAD3 to the COL1A2 collagen promoter (by ChIP). Conversely, overexpression of SMAD2 attenuates TGF-β1-induced SMAD3 phosphorylation. This identifies SMAD2 as a counterbalancing regulator of SMAD3 signaling. Conditional Smad2 knockout (renal tubular epithelial cells), ChIP on COL1A2 promoter, SMAD3 phosphorylation Western blot, nuclear translocation assay, promoter reporter assay Journal of the American Society of Nephrology : JASN High 20595680
2011 TRB3 (TRIB3) is a novel SMAD3-interacting protein; the kinase-like domain of TRB3 interacts with the MH2 domain of SMAD3. TRB3 enhances SMAD3 transcriptional activity, promotes nuclear localization of SMAD3 via MH2-domain interaction, and stabilizes phospho-SMAD3 by triggering degradation of Smurf2 (the SMAD ubiquitin regulatory factor 2). TGF-β1 stimulation or SMAD3 overexpression induces TRB3 expression, creating a positive feedback loop. Co-immunoprecipitation, domain-mapping mutagenesis, reporter assay, subcellular localization imaging, siRNA knockdown, Western blot for Smurf2/SMAD2/pSMAD3 levels Journal of cell science Medium 21896644
2011 SMAD3 directly binds to a SMAD-binding element (SBE) in the promoter region of miR-200b/a (confirmed by luciferase reporter with SBE mutagenesis) and functions as a transcriptional activator of miR-200 family members, which in turn suppress ZEB1/ZEB2 and regulate E-cadherin. This regulation occurs independently of TGF-β. Luciferase reporter assay with SBE mutagenesis, SMAD3 overexpression/silencing, miRNA profiling, ChIP (implied by binding element analysis) Oncogene Medium 22020340
2012 Activated STAT3 directly interacts with SMAD3 in vivo and in vitro, resulting in attenuation of SMAD3-SMAD4 complex formation and suppression of SMAD3 DNA-binding ability. The N-terminal region of the STAT3 DNA-binding domain is responsible for the STAT3-SMAD3 interaction and required for STAT3-mediated inhibition of TGF-β signaling. Co-immunoprecipitation in vivo and in vitro, domain mapping, SMAD3-SMAD4 complex formation assay, SMAD3 DNA-binding assay, STAT3 knockdown with TGF-β response readouts Oncogene Medium 26616859
2013 SMAD3 physically interacts with tendon transcriptional regulators Scleraxis and Mohawk (by Co-IP). Loss of Smad3 in mice reduces collagen 1 and Tenascin-C protein expression, disrupts tendon architecture, and downregulates key tendon marker genes in developing and adult tendon. Co-immunoprecipitation, Smad3-/- mouse model, histology, gene/protein expression analysis Journal of orthopaedic research Medium 23653374
2013 SMAD3 expression is sufficient (via in vivo plasmid transfection) to stimulate atrogin-1 promoter activity, inhibit Akt/mTOR signaling and protein synthesis, and induce muscle fiber atrophy. SMAD3 also inhibits PGC1α promoter activity and increases FoxO-mediated signaling and PAI-1 promoter activity. Mechanistically, SMAD3-induced decrease in miR-29 leads to increased PTEN translation, inhibiting Akt/mTOR. In vivo muscle transfection (transient transgenic), atrogin-1/PGC1α/PAI-1 promoter reporter assays, Akt/mTOR signaling Western blots, miR-29/PTEN assays Molecular endocrinology Medium 24002653
2013 WWOX protein physically interacts with SMAD3 via its WW domain 1. WWOX expression reduces SMAD3 occupancy at ANGPTL4 and SERPINE1 promoters (by ChIP), quenches TGF-β-responsive reporter activation, and causes redistribution of SMAD3 from the nuclear to the cytoplasmic compartment. Co-immunoprecipitation, GST pulldown, ChIP, luciferase reporter assay, confocal microscopy for SMAD3 localization, shRNA knockdown BMC cancer Medium 24330518
2015 Autocrine TGF-β-SMAD3 transcription factor signal (but not SMAD2) is necessary for robust TGF-β expression in dendritic cells activated by Clostridium butyricum, while SMAD2 negatively regulates TGF-β expression. This establishes that SMAD2 and SMAD3 inversely regulate TGF-β autoinduction in dendritic cells. Smad2-deficient and Smad3-deficient dendritic cells, TGF-β reporter assays, cytokine measurement, colitis model Immunity Medium 26141582
2015 PCDH1 (protocadherin-1) binds endogenously to SMAD3 in bronchial epithelial cells (confirmed by Y2H and Co-IP at endogenous levels). PCDH1 overexpression suppresses TGF-β-induced activation of a SMAD3-driven reporter and TGF-β target gene expression, while siRNA knockdown of PCDH1 increases TGF-β-induced SMAD3 transcriptional activity. Yeast two-hybrid, co-immunoprecipitation at endogenous protein levels, luciferase reporter assay, siRNA knockdown, TGF-β target gene qPCR American journal of physiology. Lung cellular and molecular physiology Medium 26209277
2017 OSM (oncostatin M)/STAT3 activation promotes SMAD3 nuclear accumulation and DNA binding in a TGF-β receptor-dependent manner. SMAD3 (but not SMAD2 or SMAD4) is required for OSM/STAT3-mediated epithelial-mesenchymal plasticity and cancer stem cell properties, establishing a STAT3-SMAD3 cooperative signaling axis. SMAD3/SMAD2/SMAD4 ablation (shRNA/CRISPR), nuclear fractionation, SMAD3-DNA binding assay, SMAD3-dependent transcriptional reporter, cancer stem cell/EMT phenotypic assays Oncogene Medium 28288136
2017 SMAD3 directly suppresses transcription of the NK cell differentiation factor E4BP4/NFIL3 (identified as a direct SMAD3 target gene), thereby inhibiting NK cell development and IFN-γ production. Disruption of SMAD3 in bone marrow expands NK cell population with enhanced tumor-suppressive activity; the SMAD3-E4BP4 axis mediates TGF-β-dependent NK cell immunosuppression. Smad3-/- bone marrow transplant, ex vivo NK cell differentiation assays, E4BP4 promoter reporter assay/ChIP, Smad3 inhibitor (SIS3) treatment, syngeneic tumor models Nature communications High 28262747
2018 Crystal structure of SMAD3 MH2 domain in complex with transcription factor FOXH1 reveals that the MH2 domain has multiple hydrophobic patches that serve as binding interfaces for different cofactors. SMAD3 and SMAD2 use different subsets of these hydrophobic patches to selectively recruit distinct cofactors (e.g., FOXH1 vs. SKI), explaining cofactor selectivity in TGF-β signaling. Crystal structure determination (X-ray crystallography) of SMAD3-FOXH1 and SMAD2-SKI complexes Science signaling High 29588413
2018 KAT5 acetyltransferase is recruited to SMAD3 by TRIB3 adaptor protein and induces phosphorylation-dependent K333 acetylation of SMAD3, which sustains SMAD3 transcriptional activity and promotes TRIB3 transcription (positive feedback loop). Metformin suppresses SMAD3 phosphorylation and decreases the KAT5/SMAD3 interaction, attenuating K333 acetylation and SMAD3-dependent transcription. Co-immunoprecipitation, in vitro acetylation assay, site-directed mutagenesis (K333), transcriptional reporter assay, metformin treatment in vivo and in vitro Oncogene Medium 29520103
2019 Macrophage-specific Smad3 knockout mice exhibit impaired phagocytic activity, defective anti-inflammatory macrophage transition, and adverse cardiac remodeling after myocardial infarction. Phagocytosis directly activates macrophage SMAD3 (independent of TGF-β release). SMAD3-null macrophages show reduced Mfge8 expression (eat-me signal), reduced IL-10 and TGF-β1 production, and attenuated PPAR expression induced by phagocytosis. Mfge8 partially rescues the phagocytic defect. Myeloid-specific Smad3 conditional knockout mice, myocardial infarction model, phagocytosis assays in vitro, cytokine measurement, Mfge8 rescue experiment Circulation research High 31092129
2020 SMAD3 directly binds to the 3'-UTR of TFEB mRNA and inhibits its transcription (confirmed by ChIP at TFEB 3'-UTR). SMAD3-mediated TFEB suppression inhibits lysosome biogenesis, leading to lysosome depletion and autophagy dysregulation in diabetic nephropathy. Pharmacological inhibition or genetic deletion of SMAD3 restores TFEB expression and lysosome biogenesis. ChIP demonstrating SMAD3 binding at TFEB 3'-UTR, SMAD3 genetic deletion/inhibition (SIS3), TFEB silencing rescue experiment, lysosome biogenesis assays (LAMP1, autophagic flux) Autophagy Medium 33043774
2021 SMAD3 binding to fibroblast differentiation gene promoters in macrophage-lineage cells (detected by ChIP-seq) drives macrophage-to-myofibroblast transition (MMT), generating cancer-associated fibroblasts. Macrophage-specific deletion or pharmacological inhibition of SMAD3 blocks MMT and suppresses CAF formation and tumor progression in vivo. ChIP-seq (SMAD3 binding), macrophage-specific Smad3 conditional KO, adoptive transfer of BMDM-derived MMTs, single-cell RNA-seq, pharmacological inhibition (SIS3), Lewis lung carcinoma model Advanced science High 34791825
2021 USP7 deubiquitinase removes mono-ubiquitin from SMAD3 (deubiquitination of SMAD3), which is required for SMAD3 DNA-binding activity. Mono-ubiquitination of SMAD3 negatively regulates its DNA-binding function; USP7-mediated de-monoubiquitination of SMAD3 facilitates SMAD3-SMAD4 dimer binding at the SMAD3 locus super-enhancer, enabling SMAD3 autoregulation. USP7 CRISPR/Cas9 KO, ChIP-seq and RNA-seq (genome-wide), cell-free and cell-based ubiquitination/deubiquitination assays, SMAD3 autoregulation reporter assay Cell death & disease Medium 34580281
2021 SO2-derived peroxymonosulfite promotes sulfenylation (cysteine oxidation) of SMAD3 at cysteine-64, inhibiting its DNA-binding activity. Mutation of Cys64 attenuates the protective effects of SO2 on angiotensin II-induced vascular remodeling and hypertension, establishing this redox modification as functionally relevant. Site-centric chemoproteomics (sulfenylation quantification), site-directed mutagenesis (Cys64), vascular smooth muscle cell assays, angiotensin II hypertension mouse model Redox biology Medium 33647858
2022 EZH2 methylates SMAD3 at K53 and K333; this methylation facilitates SMAD3 interaction with its membrane-localization molecule SARA, which in turn sustains SMAD3 phosphorylation by the TGF-β receptor. EZH2-mediated SMAD3 K53/K333 methylation is required for full SMAD3 activation upon TGF-β1 stimulation and promotes tumor metastasis. In vitro methylation assay with recombinant EZH2, site-directed mutagenesis (K53, K333), Co-IP (SMAD3-SARA interaction), TGF-β receptor phosphorylation assay, breast cancer metastasis xenograft model, TAT peptide therapeutic inhibition The Journal of clinical investigation High 35085106
2022 TGF-β/activin-activated SMAD3 (but not SMAD1) promotes SOX2 expression and anchorage-independent survival in ovarian cancer via SMAD3-dependent histone H3K4me3 recruitment at the SOX2 promoter. Conversely, BMP/SMAD1 represses SOX2 through H3K27me3 and DNA methylation. SMAD3 knockdown/knockout, ChIP for H3K4me3 at SOX2 promoter, gene expression profiling, anchorage-independent survival assays, intraperitoneal tumor burden assays Cell reports Medium 35905726
2022 SIRT2 deacetylase directly interacts with and deacetylates SMAD3 at lysine 341 and K378, reducing SMAD3 activation. SMAD3 deacetylation by SIRT2 occurs only in the presence of TGF-β and reduces SMAD3 phosphorylation, nuclear localization, and downstream fibrotic gene expression. Co-immunoprecipitation, in vitro deacetylation assay, site-directed mutagenesis (K341, K378), SIRT2 conditional KO mice, nuclear localization assays, fibrotic gene expression readouts Cell death & disease Medium 37777567
2023 SMAD3 binds to intron 3 of the AR (androgen receptor) gene to promote AR expression (identified by ChIP-seq; binding sites validated by CRISPRi). Approximately 50% of AR and SMAD3 ChIP-seq peaks overlap, indicating SMAD3 also co-occupies AR target gene loci. SMAD3 knockdown decreases AR levels and AR target gene expression, an effect partially rescued by AR re-expression. SMAD3 knockdown (siRNA), ChIP-seq (SMAD3 and AR binding), RNA-seq, CRISPRi targeting SMAD3-binding sites in AR intron 3, AR rescue experiments, SMAD3 PROTAC inhibitor Nucleic acids research High 36727462
2023 ATOH8 binds SMAD3 to form a transcriptional complex that directly represses cell cycle-promoting genes and induces oncogene-induced senescence (OIS) in lung epithelial cells downstream of Ras overactivation and TGF-β1/SMAD3 signaling. SMAD3 (not SMAD2 or SMAD4) is the determinant mediator of this senescence response. Depletion of ATOH8 accelerates Ras-driven lung tumorigenesis and confers sensitivity to SMAD3 inhibitor. Co-immunoprecipitation (ATOH8-SMAD3 complex), SMAD3/SMAD2/SMAD4 knockdown specificity assays, transcriptional profiling of repressed cell cycle genes, ATOH8 deletion mouse model, Smad3 inhibitor treatment PNAS Medium 36626550
2021 Cell intercalation downstream of TGF-β/SMAD3 signaling is required for secondary neural tube formation in vivo. SMAD3 acts with YAP to resolve a centrally positioned lumen through cell intercalation during tail bud development, demonstrated by SMAD3 loss-of-function experiments and live in vivo imaging in chicken embryo. In vivo SMAD3 loss-of-function (chick embryo electroporation), live imaging of cell intercalation, YAP inhibition assays, lumen formation readout Developmental cell Medium 33878300
2012 Linker-region phosphorylation of SMAD3 (at four sites mutated in the EPSM mutant) negatively regulates SMAD3 transcriptional activity and TGF-β1/SMAD3-induced epithelial-mesenchymal transition in renal epithelial cells. C-terminal SSXS phosphorylation is essential for mediating TGF-β response, while linker phosphorylation acts as a brake. Site-directed mutagenesis (EPSM and 3S-A SMAD3 mutants), TGF-β1 induction of EMT in Smad3-deficient primary renal cells reconstituted with mutants, Western blot and RT-PCR for EMT markers Biochemical and biophysical research communications Medium 23022526
2013 p-Akt physically interacts with SMAD3 in wild-type mouse muscles and C2C12 myoblasts (by co-immunoprecipitation). IGF-I increases p-Akt/SMAD3 interaction (retaining SMAD3 in cytoplasm), while TGF-β1 decreases it, allowing SMAD3 nuclear translocation and fibronectin expression. This p-Akt/SMAD3 interaction constitutes a molecular switch between myogenesis and fibrogenesis. Co-immunoprecipitation of p-Akt and SMAD3, IGF-I/TGF-β1 treatment, SMAD3 nuclear translocation assay, fibronectin expression, IGF-IR heterozygous KO mouse model American journal of physiology. Endocrinology and metabolism Medium 23736539

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. The EMBO journal 943 9311995
2004 Smad3 as a mediator of the fibrotic response. International journal of experimental pathology 528 15154911
2010 miR-192 mediates TGF-beta/Smad3-driven renal fibrosis. Journal of the American Society of Nephrology : JASN 314 20488955
2010 Smad2 protects against TGF-beta/Smad3-mediated renal fibrosis. Journal of the American Society of Nephrology : JASN 310 20595680
2012 SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer research 276 23139211
2008 Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling. Genes & development 219 18172167
2021 Smad3 Promotes Cancer-Associated Fibroblasts Generation via Macrophage-Myofibroblast Transition. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 178 34791825
2007 TGF-beta, Smad3 and the process of progressive fibrosis. Biochemical Society transactions 166 17635115
2017 Smad3 promotes cancer progression by inhibiting E4BP4-mediated NK cell development. Nature communications 160 28262747
2019 Macrophage Smad3 Protects the Infarcted Heart, Stimulating Phagocytosis and Regulating Inflammation. Circulation research 158 31092129
2001 SMAD3 represses androgen receptor-mediated transcription. Cancer research 157 11280774
2015 Smad2 and Smad3 Inversely Regulate TGF-β Autoinduction in Clostridium butyricum-Activated Dendritic Cells. Immunity 156 26141582
2022 Smad3 Signatures in Renal Inflammation and Fibrosis. International journal of biological sciences 150 35541902
2017 Opposing Actions of Fibroblast and Cardiomyocyte Smad3 Signaling in the Infarcted Myocardium. Circulation 150 29229611
2004 Loss of Smad3 in acute T-cell lymphoblastic leukemia. The New England journal of medicine 130 15295048
2020 circRIP2 accelerates bladder cancer progression via miR-1305/Tgf-β2/smad3 pathway. Molecular cancer 129 32019579
2011 TRB3 interacts with SMAD3 promoting tumor cell migration and invasion. Journal of cell science 119 21896644
2002 Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control. Genes & development 117 12154125
2013 Smad3 induces atrogin-1, inhibits mTOR and protein synthesis, and promotes muscle atrophy in vivo. Molecular endocrinology (Baltimore, Md.) 116 24002653
2006 Smad3 signaling involved in pulmonary fibrosis and emphysema. Proceedings of the American Thoracic Society 112 17065376
2017 Oncostatin M promotes cancer cell plasticity through cooperative STAT3-SMAD3 signaling. Oncogene 111 28288136
2005 Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3. Biochemistry 109 16156666
2006 The DNA binding activities of Smad2 and Smad3 are regulated by coactivator-mediated acetylation. The Journal of biological chemistry 100 17074756
2004 Ovarian follicle development requires Smad3. Molecular endocrinology (Baltimore, Md.) 98 15192076
2020 SMAD3 promotes autophagy dysregulation by triggering lysosome depletion in tubular epithelial cells in diabetic nephropathy. Autophagy 97 33043774
2019 Qishen granule attenuates cardiac fibrosis by regulating TGF-β /Smad3 and GSK-3β pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 96 31102891
2008 FoxL2 and Smad3 coordinately regulate follistatin gene transcription. The Journal of biological chemistry 95 19106105
2015 STAT3 selectively interacts with Smad3 to antagonize TGF-β signalling. Oncogene 90 26616859
2011 Smad3 regulates E-cadherin via miRNA-200 pathway. Oncogene 89 22020340
2007 Roles of Smad3 in TGF-beta signaling during carcinogenesis. Critical reviews in eukaryotic gene expression 89 17725494
2004 Essential role for Smad3 in regulating MCP-1 expression and vascular inflammation. Circulation research 82 14752027
2011 Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts. Cell research 81 21502976
2013 Smad3 binds Scleraxis and Mohawk and regulates tendon matrix organization. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 76 23653374
2017 Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways. World journal of gastroenterology 72 28706418
2018 Smad3-STAT3 crosstalk in pathophysiological contexts. Acta biochimica et biophysica Sinica 68 29140406
2018 Enhanced Cancer Immunotherapy with Smad3-Silenced NK-92 Cells. Cancer immunology research 67 29915022
2007 SMAD3 regulates gonadal tumorigenesis. Molecular endocrinology (Baltimore, Md.) 63 17595316
2017 Ash1l and lnc-Smad3 coordinate Smad3 locus accessibility to modulate iTreg polarization and T cell autoimmunity. Nature communications 62 28598443
2013 NFAT3 and TGF-β/SMAD3 regulate the expression of miR-140 in osteoarthritis. Arthritis research & therapy 61 24257415
2014 Negative auto-regulation of myostatin expression is mediated by Smad3 and microRNA-27. PloS one 60 24498167
2012 Phospho-specific Smad3 signaling: impact on breast oncogenesis. Cell cycle (Georgetown, Tex.) 59 22659843
2010 Smaddening complexity: the role of Smad3 in epithelial-myofibroblast transition. Cells, tissues, organs 57 21051861
2018 MicroRNA-216a induces endothelial senescence and inflammation via Smad3/IκBα pathway. Journal of cellular and molecular medicine 55 29512862
2016 Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate. PLoS genetics 54 27741240
2009 Hypoxia-activated Smad3-specific dephosphorylation by PP2A. The Journal of biological chemistry 54 19951945
2005 TGFbeta1/Smad3 counteracts BRCA1-dependent repair of DNA damage. Oncogene 53 15735739
2000 Cloning and characterization of zebrafish smad2, smad3 and smad4. Gene 53 10767528
2018 Metformin suppresses melanoma progression by inhibiting KAT5-mediated SMAD3 acetylation, transcriptional activity and TRIB3 expression. Oncogene 52 29520103
2022 Reciprocal SOX2 regulation by SMAD1-SMAD3 is critical for anoikis resistance and metastasis in cancer. Cell reports 47 35905726
2022 CircMET promotes tumor proliferation by enhancing CDKN2A mRNA decay and upregulating SMAD3. Molecular cancer 44 35042525
2022 EZH2-triggered methylation of SMAD3 promotes its activation and tumor metastasis. The Journal of clinical investigation 44 35085106
2004 Smad2 and Smad3 coordinately regulate craniofacial and endodermal development. Developmental biology 42 15183723
2015 Ponatinib ameliorates pulmonary fibrosis by suppressing TGF-β1/Smad3 pathway. Pulmonary pharmacology & therapeutics 39 26254990
2013 The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity via direct binding. BMC cancer 39 24330518
2006 Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis. Histology and histopathology 39 16528675
2020 LncRNA GAS5 attenuates fibroblast activation through inhibiting Smad3 signaling. American journal of physiology. Cell physiology 38 32374674
2006 TGF-beta and cancer: is Smad3 a repressor of hTERT gene? Cell research 38 16474430
2003 Mutation analysis of the Smad3 gene in human osteoarthritis. European journal of human genetics : EJHG 38 12939660
2003 Developmental and stage-specific expression of Smad2 and Smad3 in rat testis. Journal of andrology 37 12634305
2020 MSTN Mutant Promotes Myogenic Differentiation by Increasing Demethylase TET1 Expression via the SMAD2/SMAD3 Pathway. International journal of biological sciences 36 32210722
2016 STAT3-mediated SMAD3 activation underlies Oncostatin M-induced Senescence. Cell cycle (Georgetown, Tex.) 36 27892764
2013 Interactions between p-Akt and Smad3 in injured muscles initiate myogenesis or fibrogenesis. American journal of physiology. Endocrinology and metabolism 36 23736539
2021 Endogenous SO2-dependent Smad3 redox modification controls vascular remodeling. Redox biology 34 33647858
2023 Btg2 Promotes Focal Segmental Glomerulosclerosis via Smad3-Dependent Podocyte-Mesenchymal Transition. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 33 37749872
2021 USP7 facilitates SMAD3 autoregulation to repress cancer progression in p53-deficient lung cancer. Cell death & disease 33 34580281
2020 LncRNA Gm16410 regulates PM2.5-induced lung Endothelial-Mesenchymal Transition via the TGF-β1/Smad3/p-Smad3 pathway. Ecotoxicology and environmental safety 31 32961493
2017 Smad3 and Bmal1 regulate p21 and S100A4 expression in myocardial stromal fibroblasts via TNF-α. Histochemistry and cell biology 30 28721450
2005 Cyclosporin A treatment upregulates Id1 and Smad3 expression and delays skeletal muscle regeneration. Acta neuropathologica 30 15986223
2019 miR-145-5p attenuates hypertrophic scar via reducing Smad2/Smad3 expression. Biochemical and biophysical research communications 29 31732152
2003 Smad3 is required for enamel biomineralization. Biochemical and biophysical research communications 29 12763048
2014 Smad3: an emerging target for vocal fold fibrosis. The Laryngoscope 28 24737245
2013 Smad2 and Smad3 cooperate and antagonize simultaneously in vertebrate neurogenesis. Journal of cell science 28 24105267
2023 Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis. Experimental & molecular medicine 27 37121971
2016 Effect of transforming growth factor-β3 on the expression of Smad3 and Smad7 in tenocytes. Molecular medicine reports 27 26935007
2012 Smad3 linker phosphorylation attenuates Smad3 transcriptional activity and TGF-β1/Smad3-induced epithelial-mesenchymal transition in renal epithelial cells. Biochemical and biophysical research communications 27 23022526
2023 SIRT2 alleviated renal fibrosis by deacetylating SMAD2 and SMAD3 in renal tubular epithelial cells. Cell death & disease 26 37777567
2018 Involvement of Smad3 pathway in atrial fibrosis induced by elevated hydrostatic pressure. Journal of cellular physiology 26 29215718
2023 SMAD3 promotes expression and activity of the androgen receptor in prostate cancer. Nucleic acids research 25 36727462
2022 TGF-β1 suppresses the T-cell response in teleost fish by initiating Smad3- and Foxp3-mediated transcriptional networks. The Journal of biological chemistry 25 36581209
2002 BRCA2 and Smad3 synergize in regulation of gene transcription. Oncogene 25 12165866
2022 TGF-β1/Smad3 upregulates UCA1 to promote liver fibrosis through DKK1 and miR18a. Journal of molecular medicine (Berlin, Germany) 24 36001113
2021 Deletion of Smad3 protects against diabetic myocardiopathy in db/db mice. Journal of cellular and molecular medicine 24 33733577
2014 Neuronal and astroglial TGFβ-Smad3 signaling pathways differentially regulate dendrite growth and synaptogenesis. Neuromolecular medicine 24 24519742
2023 Tectorigenin relieved sepsis-induced myocardial ferroptosis by inhibiting the expression of Smad3. Toxicology research 23 37397920
2015 Protocadherin-1 binds to SMAD3 and suppresses TGF-β1-induced gene transcription. American journal of physiology. Lung cellular and molecular physiology 23 26209277
2014 CDK4 inhibition and doxorubicin mediate breast cancer cell apoptosis through Smad3 and survivin. Cancer biology & therapy 23 25006666
2009 BRCA1 interacts with Smad3 and regulates Smad3-mediated TGF-beta signaling during oxidative stress responses. PloS one 23 19768112
2023 FOXO3 regulates Smad3 and Smad7 through SPON1 circular RNA to inhibit idiopathic pulmonary fibrosis. International journal of biological sciences 22 37416778
2017 Sorafenib and fluvastatin synergistically alleviate hepatic fibrosis via inhibiting the TGFβ1/Smad3 pathway. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 22 29373239
2007 Smad3 and Pitx2 cooperate in stimulation of FSHbeta gene transcription. Molecular and cellular endocrinology 22 18022758
2024 NSUN5 Facilitates Hepatocellular Carcinoma Progression by Increasing SMAD3 Expression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 21 39531371
2023 ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation. Proceedings of the National Academy of Sciences of the United States of America 21 36626550
2020 SMAD3 Hypomethylation as a Biomarker for Early Prediction of Colorectal Cancer. International journal of molecular sciences 21 33036415
2018 Hydrophobic patches on SMAD2 and SMAD3 determine selective binding to cofactors. Science signaling 21 29588413
1999 Mutation analysis of the Smad3 gene in human ovarian cancers. International journal of oncology 21 10536178
2021 AMPK inhibits Smad3-mediated autoinduction of TGF-β1 in gastric cancer cells. Journal of cellular and molecular medicine 20 33538080
2010 SMAD3 and EGR1 physically and functionally interact in promoter-specific fashion. Cellular signalling 20 20149866
2023 Estrogen receptor β attenuates renal fibrosis by suppressing the transcriptional activity of Smad3. Biochimica et biophysica acta. Molecular basis of disease 19 37196860
2021 Cell intercalation driven by SMAD3 underlies secondary neural tube formation. Developmental cell 19 33878300
2019 SMAD family member 3 (SMAD3) and SMAD4 repress HIF2α-dependent iron-regulatory genes. The Journal of biological chemistry 19 30659096

Missed literature

Know a paper Affinage missed for SMAD3? Flag it for the maintainers and the community.

No submissions yet.