Affinage

TGFB1

Transforming growth factor beta-1 proprotein · UniProt P01137

Length
390 aa
Mass
44.3 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 19 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

TGFB1 is a secreted cytokine that controls cytostasis, mesenchymal/myofibroblast differentiation, extracellular matrix production, and tissue regeneration by signaling through a cell-surface serine/threonine kinase receptor system (PMID:9759503, PMID:9525694, PMID:10879283, PMID:1322148). It is produced as an inactive latent complex whose bioavailability is set extracellularly: latent TGFB1-binding proteins (LTBP1/LTBP3) are cross-linked to fibrillin by transglutaminase-2 to position latent complexes at the cell surface (PMID:35122964), αV integrins activate the latent ligand (PMID:20870411), and the metalloprotease ADAMTS6 cleaves LTBP1/LTBP3 while raising mechanotension to drive YAP/TAZ-dependent activation (PMID:36368447). Once activated, ligand binding to the type II receptor recruits and transphosphorylates the type I receptor (ALK5), which phosphorylates SMAD2/3 on C-terminal SSXS motifs; SARA anchors R-SMADs at the membrane for this step, and phosphorylated SMAD2/3 then complex with SMAD4 and translocate to the nucleus to direct target gene transcription (PMID:9759503, PMID:9525694, PMID:10879283). Signal strength and duration are tuned by an interlocking regulatory network: inhibitory SMAD7 recruits Smurf1/2 to ubiquitylate and degrade the receptor (PMID:10879283, PMID:19030025), a step opposed by the deubiquitylase USP11, which stabilizes ALK5 and amplifies SMAD2/3 phosphorylation (PMID:22773947); the CRL4 substrate receptor AMBRA1 adds nonproteolytic K63-linked ubiquitin to SMAD4 to enhance its transcriptional output (PMID:34362797); and intracellular antagonists such as TNFRSF19 block SMAD2/3 access to the receptor kinase domain (PMID:29735548). In parallel, TGFB1 engages non-SMAD effectors—Ras/ERK and SAPK/JNK/p38—that feed back on SMAD activity, mediate autoinduction through AP-1 at the TGFB1 promoter, and transduce fibrogenic signals together with effectors such as CTGF (PMID:10708950, PMID:21740331). Transcriptional feedback loops, including the Krüppel-like factor TIEG (which represses SMAD7) and induction of NUAK1/NUAK2 kinases that bind SMAD3 and ALK5, further shape responses such as cytostasis and myofibroblast contractility (PMID:12173049, PMID:30622137). Functionally, macrophage-derived TGFB1 drives a fetal-like regenerative epithelial state via YAP/TEAD and SOX9 during intestinal repair (PMID:37865088).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 High

    Established that TGFB1 acts through discrete cell-surface receptors with kinase activity, defining the receptor-based logic of the pathway.

    Evidence Receptor purification/binding assays, kinase inhibitor studies, and cloning identifying ~55 kDa type I and ~70 kDa type II receptors and the accessory proteoglycan betaglycan

    PMID:1322148

    Open questions at the time
    • Did not resolve how receptor kinases transmit signal to intracellular effectors
    • Role of betaglycan in receptor presentation only partially defined
  2. 1998 High

    Resolved the core transduction mechanism, showing how receptor activation is relayed to the nucleus via SMAD phosphorylation and complex formation.

    Evidence Pathway reconstitution, phosphorylation assays, receptor mutagenesis, and nuclear translocation studies defining type II→type I transphosphorylation and SMAD2/3 SSXS phosphorylation feeding SMAD4 complex formation

    PMID:10879283 PMID:9525694 PMID:9759503

    Open questions at the time
    • Context-specific DNA-binding partners not enumerated
    • Did not address feedback control of signal duration
  3. 2000 High

    Defined membrane anchoring and negative feedback of R-SMADs, explaining how signaling is spatially organized and self-limited.

    Evidence Co-IP, phosphorylation assays, subcellular fractionation, and gene targeting showing SARA-mediated R-SMAD anchoring and inhibitory SMAD6/7 induction as an autofeedback loop

    PMID:10879283

    Open questions at the time
    • Molecular mechanism by which inhibitory SMADs block phosphorylation not fully detailed here
  4. 2000 Medium

    Showed that TGFB1 also activates non-SMAD kinase cascades that feed back on SMAD activity and drive ligand autoinduction.

    Evidence Dominant-negative constructs, MEK inhibition, reporter and supershift assays linking Ras/ERK/SAPK, AP-1 (JunD/Fra-2) promoter binding, and Smad linker phosphorylation

    PMID:10708950

    Open questions at the time
    • Generalization beyond epithelial cells not established
    • Quantitative contribution of each kinase arm unclear
  5. 2002 Medium

    Identified a transcriptional feedback factor that amplifies SMAD signaling by repressing the inhibitory SMAD7 gene.

    Evidence SBE-luciferase reporters, endogenous p21/PAI-1 induction, Smad2 phosphorylation, and promoter-binding assays with TIEG, dependent on Smad4 and blocked by Smad7

    PMID:12173049

    Open questions at the time
    • Direct DNA-binding kinetics of TIEG at the Smad7 promoter not resolved
    • In vivo relevance not tested
  6. 2009 Medium

    Mechanistically explained receptor turnover as a brake on signaling through SMAD7-directed ubiquitylation.

    Evidence Co-IP, ubiquitylation, and receptor degradation assays showing SMAD7 recruits Smurf1/2 to degrade TGFβ receptors

    PMID:19030025

    Open questions at the time
    • Counter-regulatory deubiquitylation not addressed in this work
  7. 2010 Medium

    Placed latent ligand activation by integrins at the center of controlling TGFB1 availability.

    Evidence Cell-based activation assays with integrin loss-of-function, particularly αV integrins, on latent TGFβ complexes

    PMID:20870411

    Open questions at the time
    • Force- versus protease-dependent activation modes not disentangled here
    • Tissue-specific integrin usage unresolved
  8. 2011 Medium

    Catalogued the breadth of post-translational control over SMAD2/3 activity and stability.

    Evidence Biochemical modification assays and mutagenesis documenting phosphorylation, ubiquitination, sumoylation, acetylation, and poly(ADP)-ribosylation

    PMID:21643690

    Open questions at the time
    • Functional hierarchy among the PTMs not established
    • Enzymes for several modifications not identified
  9. 2011 Medium

    Connected canonical and non-SMAD arms to a defined fibrogenic output via myofibroblast differentiation and CTGF.

    Evidence Fibroblast transdifferentiation assays with pathway-specific kinase inhibition and loss-of-function in experimental fibrosis models

    PMID:21740331

    Open questions at the time
    • Relative dependence on ALK5/Smad3 versus MAPK/JNK/p38 context-dependent and not quantified
  10. 2012 Medium

    Identified the deubiquitylase that opposes SMAD7-driven receptor degradation, completing a ubiquitin-based rheostat on signal duration.

    Evidence Co-IP, ubiquitylation and RNAi assays showing USP11 binds SMAD7, deubiquitylates ALK5, and its catalytic activity is required to sustain SMAD2/3 phosphorylation

    PMID:22773947

    Open questions at the time
    • Single lab; in vivo physiological role not established
    • Regulation of USP11 recruitment unknown
  11. 2018 Medium

    Revealed an intracellular receptor antagonist that gates SMAD recruitment and sets TGFB1 cytostatic sensitivity.

    Evidence Co-IP with kinase-domain mapping, SMAD2/3 phosphorylation readouts, CRISPR knockout, and proliferation assays for TNFRSF19 binding to TβRI

    PMID:29735548

    Open questions at the time
    • Physiological contexts where TNFRSF19 limits signaling not defined
    • Single lab
  12. 2019 Medium

    Defined a kinase feedback module wherein TGFB1 induces NUAK1/2 that bind the signaling machinery and bidirectionally tune responses.

    Evidence ChIP, reporter assays, co-IP, and siRNA showing SMAD-responsive NUAK2 enhancer, NUAK2–SMAD3/TβRI complexes, and opposing NUAK1/NUAK2 effects on cytostasis and myofibroblast contractility

    PMID:30622137

    Open questions at the time
    • Substrates of NUAK kinases within the pathway not identified
    • Single lab
  13. 2021 Medium

    Showed nonproteolytic ubiquitylation of SMAD4 as a positive amplifier of transcriptional output with pro-metastatic consequences.

    Evidence Co-IP, K63 ubiquitylation assays, SMAD4 reporters, siRNA, and mouse tumor models for CRL4-AMBRA1

    PMID:34362797

    Open questions at the time
    • Whether this regulation operates outside breast cancer unknown
    • Single lab
  14. 2022 Medium

    Mechanistically dissected extracellular latent-complex activation through matrix cross-linking and proteolysis.

    Evidence In vitro cross-linking and structural analysis of fibrillin–LTBP1 with cell-based activation (TG2) and direct LTBP1/3 cleavage plus mechanotension/YAP-TAZ assays with catalytic mutants (ADAMTS6)

    PMID:35122964 PMID:36368447

    Open questions at the time
    • Interplay between cross-linking, proteolysis, and integrin activation not integrated
    • Single-lab studies
  15. 2023 Medium

    Demonstrated a physiological regenerative function in which macrophage-derived TGFB1 reprograms epithelium to a fetal-like state.

    Evidence Mouse genetics, organoid reconstitution, macrophage depletion, RNA-seq, and engraftment assays linking TGFB1 to YAP/TEAD and SOX9 in intestinal regeneration

    PMID:37865088

    Open questions at the time
    • Whether the same circuit operates in other regenerating tissues unknown
    • Direct versus indirect epithelial targets not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple latent-activation modes (integrins, proteases, matrix cross-linking, mechanical force) are integrated with intracellular feedback to produce context-specific, quantitatively defined outputs remains unresolved.
  • No unified model linking activation mode to downstream transcriptional program
  • Tissue-specific cofactors that direct cytostatic versus fibrogenic versus regenerative outcomes not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005576 extracellular region 2 GO:0031012 extracellular matrix 2
Pathway
R-HSA-1474244 Extracellular matrix organization 2 R-HSA-162582 Signal Transduction 2 R-HSA-1266738 Developmental Biology 1
Partners
ALK5/TGFBR1ITGAVLTBP1SMAD2SMAD3SMAD4SMAD7TNFRSF19

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 TGF-β signals through cell-surface type I and type II serine/threonine kinase receptors; ligand binding recruits and transphosphorylates the type I receptor, which then phosphorylates SMAD2/3 on C-terminal SSXS motifs, inducing their association with SMAD4 and nuclear translocation to activate target gene transcription. Biochemical pathway reconstitution, phosphorylation assays, receptor mutagenesis, nuclear translocation studies Annual review of biochemistry High 10879283 9525694 9759503
1992 TGF-β binds to cell surface receptors of 55 kDa (type I) and 70 kDa (type II); inhibitors of serine/threonine kinase activity block transcriptional and growth-inhibitory responses to TGF-β; the proteoglycan betaglycan binds TGF-β via its core protein and may regulate TGF-β interaction with signaling receptors. Receptor purification and binding assays, kinase inhibitor studies, molecular cloning, biochemical characterization Molecular reproduction and development High 1322148
2000 TGF-β activates Ras, ERKs, and SAPKs in epithelial cells; the MEK/ERK pathway is required for TGF-β autoinduction via AP-1 (JunD/Fra-2) binding to the TGFβ1 promoter; Smad3 is required for autoinduction independently of Smad4; ERK-mediated phosphorylation of the Smad1 linker region controls Smad1-Smad4 interaction and nuclear accumulation. Dominant-negative constructs (RasN17, DN-MKK4, DN-Smad3), MEK inhibitor (PD98059), reporter assays, supershift assays, promoter activity assays Cytokine & growth factor reviews Medium 10708950
2000 Receptor-regulated SMADs (SMAD2/3) are anchored to the cell membrane by SARA (Smad anchor for receptor activation); upon TGF-β stimulation they are phosphorylated by the type I receptor kinase and form oligomeric complexes with SMAD4 that translocate to the nucleus; inhibitory SMADs (SMAD6/7) block receptor-mediated R-SMAD phosphorylation and their expression is induced by TGF-β, forming a negative autofeedback loop. Co-immunoprecipitation, phosphorylation assays, subcellular fractionation, reporter assays, gene targeting Advances in immunology High 10879283
2011 TGF-β signals via the canonical ALK5/Smad3 pathway to induce myofibroblast transdifferentiation and matrix preservation; Smad-independent pathways (MAPK, JNK, p38) modulate Smad activation and can directly transduce fibrogenic signals; the downstream effector connective tissue growth factor (CTGF) mediates profibrotic actions of TGF-β. In vitro fibroblast transdifferentiation assays, kinase inhibition, loss-of-function studies in experimental models Growth factors (Chur, Switzerland) Medium 21740331
2011 SMAD2 and SMAD3 are subject to post-translational modifications including phosphorylation (C-terminal receptor-mediated and linker region by MAPKs), ubiquitination, sumoylation, acetylation, and poly(ADP)-ribosylation that regulate their activity and stability. Biochemical modification assays, mutagenesis, proteasomal degradation studies Cell and tissue research Medium 21643690
2012 USP11 deubiquitylase interacts with SMAD7 and deubiquitylates the type I TGF-β receptor (ALK5), thereby stabilizing it and enhancing TGF-β-induced SMAD2/3 phosphorylation and transcriptional responses; RNAi depletion of USP11 inhibits SMAD2/3 phosphorylation, and USP11 deubiquitylase activity is required for this effect. Co-immunoprecipitation, ubiquitylation assays, RNAi knockdown, SMAD2/3 phosphorylation assays, reporter assays Open biology Medium 22773947
2010 TGF-β is produced as an inactive (latent) complex that must be activated to bind its receptor; members of the integrin receptor family (particularly αV integrins) play crucial roles in activating latent TGFβ, controlling its availability to signal. Cell-based TGF-β activation assays, integrin loss-of-function studies, biochemical activation assays Trends in biochemical sciences Medium 20870411
2022 Latent TGFβ binding proteins (LTBPs) are cross-linked by transglutaminase-2 (TG2) to fibrillin in the extracellular matrix; TG2 cross-links LTBP-1 and LTBP-3 to fibrillin, and the resulting fibrillin-LTBP1 complex shows a perpendicular arrangement; cross-linking does not alter integrin αVβ6 interaction with latent TGFβ but increases TGFβ activation in cell-based assays, likely by directing latent complexes to the cell surface. In vitro cross-linking assays, structural analysis of fibrillin-LTBP1 complex, cell-based TGFβ activation assays, heparan sulphate competition experiments Matrix biology : journal of the International Society for Matrix Biology Medium 35122964
2022 ADAMTS6 metalloprotease directly cleaves LTBP1 and LTBP3, components of the large latent TGFβ complex, and binds these complexes; ADAMTS6 expression also increases cellular mechanotension, leading to YAP/TAZ nuclear translocation; both mechanisms contribute to TGFβ activation from large latent complexes, and catalytic activity of ADAMTS6 is required for effective TGFβ activation. Cell-based TGFβ activation assays, proteolytic cleavage assays, mechanotension measurements, YAP/TAZ localization assays, catalytic mutant analysis Matrix biology : journal of the International Society for Matrix Biology Medium 36368447
2019 TGF-β transcriptionally induces NUAK1 and NUAK2 kinases via SMAD2/3/4 and MAPK pathways; a SMAD-responsive enhancer within the first intron of NUAK2 recruits SMAD proteins; NUAK2 forms protein complexes with SMAD3 and the TGFβ type I receptor; NUAK1 negatively and NUAK2 positively regulate TGFβ-induced cytostasis, mesenchymal differentiation, and myofibroblast contractility. Chromatin immunoprecipitation, reporter assays, co-immunoprecipitation, siRNA knockdown, cell functional assays The Journal of biological chemistry Medium 30622137
2018 TNFRSF19 binds the kinase domain of TGFβ type I receptor (TβRI) in the cytoplasm, blocking association of SMAD2/3 with TβRI and subsequent phosphorylation; ectopic TNFRSF19 expression confers resistance to TGFβ-induced cell-cycle arrest; TNFRSF19 knockout unleashes SMAD2/3 phosphorylation and TGFβ target gene transcription. Co-immunoprecipitation, kinase domain interaction mapping, SMAD2/3 phosphorylation assays, CRISPR knockout, proliferation assays Cancer research Medium 29735548
2021 AMBRA1 serves as the substrate receptor in the CUL4-RING ubiquitin ligase (CRL4) complex and mediates nonproteolytic K63-linked polyubiquitylation of SMAD4, enhancing its transcriptional activity; AMBRA1 potentiates TGFβ signaling and promotes TGFβ-induced EMT, migration, and invasion in breast cancer cells and metastasis in mouse models. Co-immunoprecipitation, ubiquitylation assays, SMAD4 transcriptional reporter assays, siRNA knockdown, mouse tumor models Cancer research Medium 34362797
2002 TIEG (TGF-β inducible early gene), a Krüppel-like transcription factor, enhances TGFβ/SMAD-dependent transcription by binding and repressing the Smad7 gene promoter; TIEG overexpression enhances TGFβ-induced Smad2 phosphorylation and induction of p21 and PAI-1; this effect requires Smad4 and is blocked by Smad7 overexpression. Reporter assays (SBE-luciferase), endogenous gene expression assays, Smad2 phosphorylation assays, promoter binding assays Oncogene Medium 12173049
2023 TGFB1 is necessary and sufficient to induce a fetal-like/regenerative transcriptional state in intestinal organoids; mechanistically, TGFB1 activates pro-regenerative factors YAP/TEAD and SOX9 in the epithelium; macrophage-derived TGFB1 surge at 2 days post-irradiation mediates intestinal regeneration, and genetic disruption of TGFB signaling or macrophage depletion impairs the regenerative response. Mouse genetics, organoid culture, macrophage depletion, RNA sequencing, TGFB1 treatment, in vivo engraftment assays Cell stem cell Medium 37865088
2009 SMAD7 recruits E3 ubiquitin ligases (Smurf1/2) to TGFβ receptors, targeting them for ubiquitin-mediated proteasomal degradation, thereby negatively regulating TGFβ receptor stability and duration of signaling. Co-immunoprecipitation, ubiquitylation assays, receptor degradation assays, knockdown studies Cell research Medium 19030025
2018 TGFβ1 stimulation of monocytes induces expression of integrin subunits ITGA5 and ITGAV (but lowers ITGB8), establishing a feedback regulatory loop; in SSc patients, reduced expression of TGFβ-activating integrins (ITGA5, ITGAV, ITGB3, ITGB5, ITGB8) on monocytes correlates with decreased TGFβ activation in serum despite normal total TGFβ levels. Luciferase TGFβ reporter assays on primary fibroblasts, rhTGFβ1 stimulation, TGFBR1 inhibitor (SB-505124), qPCR of integrin expression, acid activation of serum Arthritis research & therapy Low 32143707
2015 Intermittent compressive mechanical force applied to human periodontal ligament (hPDL) fibroblasts promotes intracellular accumulation (not secretion) of TGF-β1, which then drives expression of SOST and POSTN; blocking TGF-β1 with a neutralizing antibody or TGFβ receptor inhibitor (SB431542) attenuates force-induced SOST and POSTN expression. Compressive force loading, cycloheximide treatment, TGFβR1 inhibitor (SB431542), neutralizing antibody, ELISA, Western blot, RT-PCR Journal of dental research Low 25870205
2018 TGF-β1 and hypoxia enhance glucose metabolism and lactate production in tendon cells via HIF1A signaling, activating a Warburg-type glycolytic reprogramming; this was shown both in vivo (murine TGF-β1 injection model) and in vitro in tendon explants. In vivo murine injection, in vitro tendon explant culture, immunohistochemistry, gene expression profiling Connective tissue research Low 29447016

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 TGF-beta signal transduction. Annual review of biochemistry 3811 9759503
2008 TGFbeta in Cancer. Cell 3337 18662538
2012 TGFβ signalling in context. Nature reviews. Molecular cell biology 2648 22992590
2011 TGF-β signaling in fibrosis. Growth factors (Chur, Switzerland) 992 21740331
1992 Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 751 1560823
2009 Roles of TGFbeta in metastasis. Cell research 713 19050696
2020 TGF-β Signaling. Biomolecules 664 32210029
2006 The logic of TGFbeta signaling. FEBS letters 615 16678165
1997 Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science (New York, N.Y.) 540 9027312
2014 Targeting the TGFβ pathway for cancer therapy. Pharmacology & therapeutics 514 25444759
2001 CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 484 11163239
1990 The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death. Developmental biology 473 2307287
2012 The TGFbeta superfamily signaling pathway. Wiley interdisciplinary reviews. Developmental biology 445 23799630
2012 Regulation of EMT by TGFβ in cancer. FEBS letters 429 22710176
2000 TGF-beta signaling by Smad proteins. Advances in immunology 419 10879283
2000 Role of Ras and Mapks in TGFbeta signaling. Cytokine & growth factor reviews 372 10708950
2005 TGF-beta and cancer. Cytokine & growth factor reviews 360 16289860
2000 CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans. Nature cell biology 347 10707082
1998 C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 315 9548255
1997 Interaction and regulation of subcellular localization of CED-4 by CED-9. Science (New York, N.Y.) 304 9027313
2011 Role of Smads in TGFβ signaling. Cell and tissue research 295 21643690
1997 Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature 267 9024666
1990 TGF-beta: problems and prospects. Cell regulation 266 2100192
2006 TGFbeta pathobiology in the eye. Laboratory investigation; a journal of technical methods and pathology 244 16341020
1998 Essential role of CED-4 oligomerization in CED-3 activation and apoptosis. Science (New York, N.Y.) 225 9721101
2010 TGFβ: a sleeping giant awoken by integrins. Trends in biochemical sciences 184 20870411
2005 Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans. Nature 178 16208361
2003 Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. Science (New York, N.Y.) 164 14645848
2001 Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium-mediated killing. Proceedings of the National Academy of Sciences of the United States of America 164 11226309
2009 Regulating the stability of TGFbeta receptors and Smads. Cell research 162 19030025
1997 Caenorhabditis elegans CED-4 stimulates CED-3 processing and CED-3-induced apoptosis. Current biology : CB 157 9210374
2002 TGFbeta inducible early gene enhances TGFbeta/Smad-dependent transcriptional responses. Oncogene 124 12173049
2008 Caenorhabditis elegans drp-1 and fis-2 regulate distinct cell-death execution pathways downstream of ced-3 and independent of ced-9. Molecular cell 121 18722182
1999 TGF-beta and cancer. Microbes and infection 119 10611761
2005 TGF-beta signaling in chondrocytes. Frontiers in bioscience : a journal and virtual library 110 15569609
2008 Phagocytic receptor CED-1 initiates a signaling pathway for degrading engulfed apoptotic cells. PLoS biology 107 18351800
1992 TGF-beta receptors. Molecular reproduction and development 106 1322148
2006 Transforming growth factor beta (TGFbeta) and keloid disease. International journal of surgery (London, England) 104 17660136
1997 Caenorhabditis elegans CED-9 protein is a bifunctional cell-death inhibitor. Nature 104 9384385
2012 USP11 augments TGFβ signalling by deubiquitylating ALK5. Open biology 100 22773947
2000 The ced-8 gene controls the timing of programmed cell deaths in C. elegans. Molecular cell 100 10882128
2023 LYC inhibits the AKT signaling pathway to activate autophagy and ameliorate TGFB-induced renal fibrosis. Autophagy 97 38037248
1998 Caenorhabditis elegans EGL-1 disrupts the interaction of CED-9 with CED-4 and promotes CED-3 activation. The Journal of biological chemistry 91 9837929
2019 A New Switch for TGFβ in Cancer. Cancer research 89 31300476
1998 TGF-beta: a balancing act. International reviews of immunology 88 9646177
2004 Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4. Molecular cell 84 15383288
2023 TGFB1 induces fetal reprogramming and enhances intestinal regeneration. Cell stem cell 80 37865088
1998 TGF-beta receptors and signalling mechanisms. Mineral and electrolyte metabolism 79 9525694
2020 TGFβ-Directed Therapeutics: 2020. Pharmacology & therapeutics 78 32835827
2012 The core apoptotic executioner proteins CED-3 and CED-4 promote initiation of neuronal regeneration in Caenorhabditis elegans. PLoS biology 77 22629231
2012 CED-1, CED-7, and TTR-52 regulate surface phosphatidylserine expression on apoptotic and phagocytic cells. Current biology : CB 74 22727702
2005 TGF-beta signaling. WormBook : the online review of C. elegans biology 73 18050404
2010 The Wnt pathway controls cell death engulfment, spindle orientation, and migration through CED-10/Rac. PLoS biology 71 20126385
2019 TGFB-INHB/activin signaling regulates age-dependent autophagy and cardiac health through inhibition of MTORC2. Autophagy 66 31884871
2019 RNA sequencing reveals MMP2 and TGFB1 downregulation in LRRK2 G2019S Parkinson's iPSC-derived astrocytes. Neurobiology of disease 58 31085228
2001 Altered expression of TGFB receptors and mitogenic effects of TGFB in pancreatic carcinomas. International journal of oncology 55 11408925
2007 New rationales for using TGFbeta inhibitors in radiotherapy. International journal of radiation biology 54 18058368
2016 The archaeal Ced system imports DNA. Proceedings of the National Academy of Sciences of the United States of America 53 26884154
2011 Evidence that CED-9/Bcl2 and CED-4/Apaf-1 localization is not consistent with the current model for C. elegans apoptosis induction. Cell death and differentiation 52 21886181
2015 Mechanical Force-induced TGFB1 Increases Expression of SOST/POSTN by hPDL Cells. Journal of dental research 48 25870205
2000 The significance of CD105, TGFbeta and CD105/TGFbeta complexes in coronary artery disease. Atherosclerosis 48 10996361
2012 TGFβ signaling in liver regeneration. Current pharmaceutical design 44 22630085
2018 TNFRSF19 Inhibits TGFβ Signaling through Interaction with TGFβ Receptor Type I to Promote Tumorigenesis. Cancer research 42 29735548
2016 Mechanobiology of TGFβ signaling in the skeleton. Matrix biology : journal of the International Society for Matrix Biology 42 26877077
2018 Optimal Hypoxia Regulates Human iPSC-Derived Liver Bud Differentiation through Intercellular TGFB Signaling. Stem cell reports 39 30033085
2020 Multifaceted transforming growth factor-beta (TGFβ) signalling in glioblastoma. Cellular signalling 37 32320860
2011 TGFB1 and IL8 gene polymorphisms and susceptibility to visceral leishmaniasis. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 37 21376140
2008 TGFbeta promotes Wnt expression during cataract development. Experimental eye research 37 18789926
2006 Restriction of vaccinia virus replication by a ced-3 and ced-4-dependent pathway in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America 37 16537504
2019 Transforming Growth Factor-Beta (TGFβ) Signaling Pathway in Cholangiocarcinoma. Cells 34 31450767
2022 circ_0006089 promotes gastric cancer growth, metastasis, glycolysis, and angiogenesis by regulating miR-361-3p/TGFB1. Cancer science 33 35347818
2020 High-Fat Diet Promotes DSS-Induced Ulcerative Colitis by Downregulated FXR Expression through the TGFB Pathway. BioMed research international 32 33029504
2019 Transforming growth factor β (TGFβ) induces NUAK kinase expression to fine-tune its signaling output. The Journal of biological chemistry 32 30622137
2022 Latent TGFβ complexes are transglutaminase cross-linked to fibrillin to facilitate TGFβ activation. Matrix biology : journal of the International Society for Matrix Biology 30 35122964
2021 Genetic and Epigenetic Fine-Tuning of TGFB1 Expression Within the Human Osteoarthritic Joint. Arthritis & rheumatology (Hoboken, N.J.) 30 33760378
2019 Structural biology of the TGFβ family. Experimental biology and medicine (Maywood, N.J.) 30 31594405
2013 Mechanistic insights into CED-4-mediated activation of CED-3. Genes & development 30 24065769
2011 The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5-CED-12 in C. elegans. Development (Cambridge, England) 29 21490059
1998 Expression of ced-3 and ced-9 homologs in Alzheimer's disease cerebral cortex. Neuroscience letters 29 9572587
2022 The radiobiology of TGFβ. Seminars in cancer biology 27 35122974
2010 Myocardial fibrosis and TGFB expression in hyperhomocysteinemic rats. Molecular and cellular biochemistry 27 20938722
2003 TGF-beta: how tolerant can it be? Immunologic research 27 14713712
1998 TGF-beta and calcitriol. General pharmacology 27 9502167
2020 The microRNAs miR-302d and miR-93 inhibit TGFB-mediated EMT and VEGFA secretion from ARPE-19 cells. Experimental eye research 26 32980316
2001 Expression of PDGF-A, TGFb and VCAM-1 during the developmental stages of experimental atherosclerosis. European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes 26 11684832
1998 Caenorhabditis elegans anti-apoptotic gene ced-9 prevents ced-3-induced cell death in Drosophila cells. Journal of cell science 25 9471995
1997 Mutational analysis of the interacting cell death regulators CED-9 and CED-4. Cell death and differentiation 25 14555965
1996 TGF-beta and functional differentiation. Journal of mammary gland biology and neoplasia 25 10887508
2018 Aberrant DNA methylation of Tgfb1 in diabetic kidney mesangial cells. Scientific reports 23 30397232
2013 Expression of Clu and Tgfb1 during murine tooth development: effects of in-vivo transfection with anti-miR-214. European journal of oral sciences 23 23841781
2018 TGF-b1 or hypoxia enhance glucose metabolism and lactate production via HIF1A signaling in tendon cells. Connective tissue research 22 29447016
2016 WFIKKN1 and WFIKKN2: "Companion" proteins regulating TGFB activity. Cytokine & growth factor reviews 22 27325460
2006 2:1 Stoichiometry of the CED-4-CED-9 complex and the tetrameric CED-4: insights into the regulation of CED-3 activation. Cell cycle (Georgetown, Tex.) 22 16294007
2022 ADAMTS6 cleaves the large latent TGFβ complex and increases the mechanotension of cells to activate TGFβ. Matrix biology : journal of the International Society for Matrix Biology 21 36368447
2021 Attenuated TGFB signalling in macrophages decreases susceptibility to DMBA-induced mammary cancer in mice. Breast cancer research : BCR 21 33761981
2021 AMBRA1 Promotes TGFβ Signaling via Nonproteolytic Polyubiquitylation of Smad4. Cancer research 21 34362797
2019 TGFB1-driven mesenchymal stem cell-mediated NIS gene transfer. Endocrine-related cancer 21 30121623
2011 Tissue-specific organelle DNA degradation mediated by DPD1 exonuclease. Plant signaling & behavior 21 21852754
2020 TGFβ-mediated expression of TGFβ-activating integrins in SSc monocytes: disturbed activation of latent TGFβ? Arthritis research & therapy 20 32143707
2012 Mutations defective in ribonucleotide reductase activity interfere with pollen plastid DNA degradation mediated by DPD1 exonuclease. The Plant journal : for cell and molecular biology 20 22239102

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