Affinage

SUFU

Suppressor of fused homolog · UniProt Q9UMX1

Length
484 aa
Mass
53.9 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUFU is an essential negative regulator of Hedgehog (Hh) signaling that controls the activity, localization, and stability of GLI/Ci transcription factors through multiple mechanisms. SUFU binds GLI proteins via N-terminal (SIN) and C-terminal (SIC) interaction sites: SIN-mediated binding sequesters GLI in the cytoplasm by competing with importin β1 for overlapping GLI binding sites, while SIC-mediated binding inhibits GLI transcriptional activity in the nucleus by masking the CBP co-activator site and recruiting the NuRD repressor component p66β; SUFU also recruits GSK3β into a trimolecular complex with Gli3 to promote Gli3 processing into a transcriptional repressor (PMID:25941387, PMID:25403183, PMID:19622347, PMID:24854174). Upon Hh stimulation, SuFu–Gli complexes translocate to primary cilia where they dissociate, freeing Gli for nuclear entry, while SUFU itself is subject to dynamic regulation through stabilizing phosphorylation (PKA/GSK3β at Ser-342/Ser-346), proteolytic ubiquitylation (Fbxl17 at K257), and non-proteolytic K63-linked ubiquitylation (Itch/β-arrestin2 promoting Gli3 repressor formation), as well as through ERK2- and PRMT7-mediated modifications on GLI that weaken the SUFU–GLI interaction (PMID:20956384, PMID:21317289, PMID:27234298, PMID:29515120, PMID:35831023, PMID:31000813). Beyond Hh signaling, SUFU suppresses WNT/β-catenin signaling by promoting β-catenin nuclear export, inhibits NF-κB-mediated inflammation by preventing TRAF6 phase separation and autoubiquitination, retains ZNF281 in the cytoplasm to suppress tumor cell migration, and its loss-of-function causes medulloblastoma predisposition and Joubert syndrome (PMID:15077159, PMID:37441604, PMID:36220888, PMID:12068298, PMID:28965847).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 High

    Establishing SUFU as a nuclear export factor for GLI and a tumor suppressor: truncating SUFU mutations in medulloblastoma patients abolished GLI nuclear export, revealing that SUFU's core function is cytoplasmic sequestration of GLI transcription factors and that its loss causes constitutive Hh pathway activation and tumor predisposition.

    Evidence Functional analysis of germline/somatic truncating mutations from medulloblastoma patients, nuclear localization assays; co-IP, Far Western, and mutagenesis identifying the SYGH motif in GLI and the C-terminal 19 residues of SUFU as critical for binding

    PMID:12068298 PMID:12426310

    Open questions at the time
    • Mechanism of SUFU-mediated nuclear export not identified (e.g., exportin involvement)
    • Whether SUFU acts on all three GLI family members identically was unknown
  2. 2004 Medium

    Extending SUFU function beyond Hedgehog: SUFU was shown to promote β-catenin nuclear export, establishing a cross-talk role in suppressing WNT signaling, and SAP18/Galectin3 were identified as interactors influencing SUFU subcellular localization.

    Evidence Medulloblastoma-derived SUFU truncation mutant failed to decrease nuclear β-catenin or inhibit Tcf/LEF reporter; yeast two-hybrid and co-IP identified SAP18 and Galectin3 as binding partners with localization consequences

    PMID:14611647 PMID:15077159

    Open questions at the time
    • Direct mechanism of β-catenin export by SUFU not elucidated
    • SAP18 and Galectin3 interactions not independently validated in additional systems
  3. 2006 High

    Identifying GSK3β as a kinase that phosphorylates SUFU and modulates its GLI-binding capacity, and showing that Drosophila Su(fu) co-enters the nucleus with Ci in response to Hh, revealing that SUFU is not purely a cytoplasmic anchor but also functions at nuclear targets.

    Evidence Mass spectrometry-identified GSK3β as SUFU-binding partner; in vitro kinase assay, phosphomimetic mutants with impaired Gli1 binding; Drosophila immunofluorescence and NLS mutant analysis

    PMID:16595130 PMID:17182001

    Open questions at the time
    • Specific GSK3β phosphorylation sites on SUFU not yet mapped
    • Whether nuclear entry of Su(fu)-Ci complex is conserved in mammals was untested
  4. 2008 High

    Demonstrating that Hh signaling promotes SUFU degradation via ubiquitylation at K257, establishing regulated protein turnover as a key mechanism for relieving GLI repression.

    Evidence Ubiquitylation assay identifying K257, K257R stabilizing mutant showing enhanced repressor and growth-inhibitory activity

    PMID:18997815

    Open questions at the time
    • E3 ligase responsible for K257 ubiquitylation not yet identified in this study
    • Whether K257 ubiquitylation is the sole degradative signal was unclear
  5. 2009 High

    Revealing that SUFU controls full-length GLI protein levels in a cilium-independent manner by antagonizing the degradation factor Spop, and that SUFU recruits GSK3β into a trimolecular complex with Gli3 essential for Gli3 repressor processing—two mechanistically distinct regulatory arms.

    Evidence Sufu-knockout MEFs with cross-species rescue; co-IP of Gli3/Sufu/GSK3β trimolecular complex, in vitro kinase assay, Shh-induced complex dissociation

    PMID:19622347 PMID:19684112

    Open questions at the time
    • How Sufu antagonizes Spop at the molecular level was not resolved
    • Whether the trimolecular complex operates identically for Gli2 was not tested
  6. 2010 High

    Live imaging revealed that Hh stimulation rapidly recruits endogenous SuFu–Gli complexes to primary cilia where they dissociate, directly linking ciliary dynamics to GLI activation and showing PKA blocks this recruitment.

    Evidence Live-cell imaging of endogenous SuFu–Gli, pharmacological PKA manipulation, cilia fluorescence microscopy

    PMID:20956384

    Open questions at the time
    • Signal that triggers ciliary recruitment of the complex was not identified
    • Fate of SuFu after ciliary dissociation (recycling vs. degradation) was unclear
  7. 2011 High

    Mapping the dual PKA (Ser-346) and GSK3β (Ser-342) phosphorylation sites on SUFU that stabilize it against Hh-induced degradation, and showing that these phosphorylations regulate SUFU ciliary residence time and Gli2/3 ciliary localization.

    Evidence Site-directed mutagenesis of S342/S346, phosphomimetic mutants, PKA inhibitors, primary cilia imaging

    PMID:21317289

    Open questions at the time
    • Phosphatase(s) that dephosphorylate Ser-342/346 upon Hh activation not identified
    • Quantitative contribution of each site to stability vs. localization not resolved
  8. 2012 High

    Genetic epistasis showed Kif7's positive role in Hh signaling operates through restricting SUFU inhibitory activity: halving Sufu dosage rescued Kif7-null phenotypes, positioning SUFU as the rate-limiting repressor downstream of cilia-associated regulators.

    Evidence Mouse Kif7-null crossed with Sufu heterozygous, rescue of Hh pathway activity, primary cilia immunofluorescence

    PMID:21795282

    Open questions at the time
    • Molecular mechanism by which Kif7 promotes Sufu turnover or ciliary exclusion not resolved
  9. 2013 High

    The crystal structure of full-length SUFU and its complex with the GLI SYGHL motif revealed that GLI binding induces major conformational rearrangement including restructuring of an intrinsically disordered loop, providing the first atomic-level framework for understanding SUFU-GLI regulation.

    Evidence X-ray crystallography and SAXS of full-length human SUFU ± GLI peptide

    PMID:24311597

    Open questions at the time
    • Structure of SUFU bound to full-length GLI (beyond peptide) not determined
    • How conformational change relates to pathway-dependent dissociation not structurally resolved
  10. 2014 High

    Defining the nuclear repressive mechanism: SUFU recruits the NuRD component p66β to GLI on Hh target gene promoters, while importin β1 competes with SUFU for overlapping GLI N-terminal binding sites, establishing a competition model governing GLI nuclear-cytoplasmic partitioning.

    Evidence SUFU interactome proteomics, ChIP on endogenous Hh promoters, zebrafish epistasis; quantitative live imaging and direct binding affinity measurements for importin β1 vs. SUFU on GLI1

    PMID:24854174 PMID:25403183

    Open questions at the time
    • Whether importin β1 competition operates for Gli2/3 equivalently was not tested
    • Structural basis of the overlapping binding sites not resolved
  11. 2015 High

    Dual-site binding model consolidated: SIN-mediated binding drives cytoplasmic sequestration while SIC-mediated binding masks the CBP co-activator site for nuclear repression, and SUFU differentially stabilizes Gli1 (by antagonizing Numb/Itch) vs. Gli2/3 (by antagonizing Spop).

    Evidence Drosophila genetic epistasis with SIN/SIC site mutagenesis and reporter assays; Sufu-deficient mouse lung with Gli protein level analysis

    PMID:24886827 PMID:25941387

    Open questions at the time
    • How SIN and SIC binding are coordinated temporally during pathway activation remains unclear
    • Structural basis for SIC masking of CBP site not determined
  12. 2016 High

    Fbxl17 was identified as the nuclear E3 ligase targeting SUFU for proteolytic degradation, and a medulloblastoma-associated SUFU mutation was shown to enhance Fbxl17-mediated turnover, directly linking SUFU ubiquitylation to tumor pathogenesis.

    Evidence Co-IP, ubiquitylation assay, Fbxl17 shRNA depletion, medulloblastoma patient mutation analysis and tumor growth assay

    PMID:27234298

    Open questions at the time
    • Whether Fbxl17 acts on K257 specifically was not determined
    • Regulation of Fbxl17 itself by Hh signaling not characterized
  13. 2017 High

    Two unexpected inputs into SUFU regulation were discovered: BCL-2 family anti-apoptotic proteins directly bind a BH domain in SUFU to promote its turnover and inhibit SUFU-GLI interaction in a feedforward loop, and homozygous hypomorphic SUFU missense variants cause Joubert syndrome by destabilizing SUFU and impairing GLI3 repressor formation.

    Evidence Co-IP of BCL-2/MCL-1/BCL-XL with SUFU, BH3 mimetic pharmacological rescue; patient fibroblast functional studies for Joubert syndrome variants with SUFU stability, GLI3 binding, and GLI3R processing readouts

    PMID:28945232 PMID:28965847

    Open questions at the time
    • Structural basis for BH domain interaction with SUFU not resolved
    • Whether Joubert-associated variants affect non-Hh functions of SUFU untested
  14. 2018 High

    A non-proteolytic regulatory layer was uncovered: Itch/β-arrestin2 catalyzes K63-linked polyubiquitylation of SUFU, which strengthens SUFU–Gli3 association and promotes Gli3 repressor formation, with Hh signaling antagonizing this modification.

    Evidence K63-specific ubiquitylation assay, reciprocal co-IP, Gli3 repressor processing assay, medulloblastoma patient mutation functional analysis

    PMID:29515120

    Open questions at the time
    • Specific lysine residue(s) on SUFU targeted by K63-linked ubiquitylation not mapped
    • Whether K63-ub SUFU has altered ciliary dynamics is unknown
  15. 2019 High

    Post-translational modification of GLI itself modulates SUFU binding: PRMT7-mediated methylation of GLI2 at R225/R227 near the SUFU-binding region reduces GLI2-SUFU interaction, identifying arginine methylation as a new mechanism for pathway activation.

    Evidence In vitro methylation assay, site-directed mutagenesis, co-IP, reporter assay, PRMT7-deficient MEFs

    PMID:31000813

    Open questions at the time
    • Whether PRMT7-mediated methylation is Hh-signal-dependent not established
    • Effect of R225/R227 methylation on GLI2 ciliary localization not tested
  16. 2022 High

    ERK2 multisite phosphorylation of GLI1 near the SUFU-binding site cooperatively weakens SUFU-GLI1 affinity >25-fold, linking RAS/MAPK signaling to Hh pathway derepression; separately, SUFU retains ZNF281 in the cytoplasm by masking its NLS in a Hedgehog-independent manner, and SUFU associates with LATS1 to regulate a YAP-ACSL4 ferroptosis axis.

    Evidence In vitro kinase assay with recombinant ERK2, quantitative binding affinity, phosphomimetic mutagenesis; co-IP and ChIP for ZNF281; co-IP and deletion mapping for LATS1 with ferroptosis sensitivity assays

    PMID:35800779 PMID:35831023 PMID:36220888

    Open questions at the time
    • Whether ERK2 phosphorylation occurs on endogenous GLI1 in vivo not shown
    • SUFU-LATS1 interaction mechanism and Hippo pathway cross-talk details remain superficial
    • ZNF281 retention by SUFU validated only in cancer cell lines
  17. 2023 High

    SUFU was shown to suppress NF-κB-mediated inflammation by directly inhibiting TRAF6 liquid-liquid phase separation and autoubiquitination, extending SUFU's suppressive role to innate immune signaling.

    Evidence In vitro phase separation assay with purified proteins, FRAP, native-PAGE, myeloid-specific Sufu knockout mice, LPS/CLP in vivo inflammation models

    PMID:37441604

    Open questions at the time
    • Whether SUFU-TRAF6 interaction is regulated by Hh signaling not tested
    • Structural basis of SUFU inhibition of TRAF6 phase separation unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions remain: the structural basis for full-length GLI binding and signal-dependent SUFU-GLI dissociation at cilia; how proteolytic (Fbxl17) and non-proteolytic (Itch/K63) ubiquitylation are coordinated; whether SUFU's non-Hh functions (WNT, NF-κB, Hippo, ZNF281) are interdependent or independently regulated; and the identity of the phosphatase(s) that reverse PKA/GSK3β stabilizing phosphorylation on SUFU.
  • No structure of SUFU bound to full-length GLI exists
  • Coordination of K48 vs. K63 ubiquitylation on SUFU unresolved
  • Phosphatase(s) acting on Ser-342/Ser-346 unidentified
  • Whether non-Hh functions of SUFU operate in the same tissues/developmental contexts is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0060090 molecular adaptor activity 3
Localization
GO:0005829 cytosol 6 GO:0005634 nucleus 5 GO:0005929 cilium 3
Pathway
R-HSA-162582 Signal Transduction 16 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 2
Partners
FBXL17GATD3BGLI1GLI2GLI3GSK3BITCHTRAF6
Complex memberships
Gli3/SUFU/GSK3β trimolecular complexSUFU-GLI complexSUFU-Itch/β-arrestin2 complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 SUFU exports the GLI transcription factor from nucleus to cytoplasm; truncating mutations in SUFU abolish this nuclear export activity, leading to constitutive activation of SHH signaling and predisposition to medulloblastoma. Functional analysis of truncating mutants from germline/somatic mutations in medulloblastoma patients; nuclear localization assay of mutant proteins Nature genetics High 12068298
2002 SUFU directly interacts with GLI proteins through a conserved SYGH motif in GLI/Ci; specifically, Gly122 and His123 within this motif are critical for SUFU binding. A C-terminal 19-amino-acid deletion in SUFU (Δ465) abrogates GLI1 binding and causes nuclear localization of SUFU. Co-immunoprecipitation, Far Western assay, truncation analysis and mutagenesis The Journal of biological chemistry High 12426310
2010 Hedgehog stimulation rapidly recruits endogenous SuFu-Gli complexes to primary cilia, where they dissociate, allowing Gli to enter the nucleus and activate transcription. PKA activation blocks ciliary localization of SuFu-Gli complexes and prevents their dissociation. Live-cell imaging of endogenous SuFu-Gli complexes; pharmacological manipulation of PKA; fluorescence microscopy of cilia localization The Journal of cell biology High 20956384
2009 Sufu controls protein levels of full-length Gli transcription factors (affecting both Gli activator and repressor production) in a cilium-independent manner by antagonizing Spop, a Gli-degrading factor. This regulation is evolutionarily conserved, as zebrafish and fly Sufu restore Gli protein function in Sufu-deficient mammalian cells. Genetic loss-of-function in mouse (Sufu-deficient cells), rescue with orthologous Sufu proteins from zebrafish and fly, Western blot for Gli protein levels Genes & development High 19684112
2009 Sufu mediates phosphorylation of Gli3 by GSK3β through formation of a trimolecular Gli3/Sufu/GSK3β complex, which is essential for Gli3 processing into a transcriptional repressor. Sonic Hh stimulation dissociates the Sufu/GSK3β complex from Gli3, blocking Gli3 processing. Co-immunoprecipitation of trimolecular complex, Sufu-/- mouse embryonic fibroblasts, siRNA knockdown, in vitro kinase assay Biochemical and biophysical research communications High 19622347
2004 Mouse Sufu interacts with the nuclear co-repressor SAP18 (Sin3-associated polypeptide 18) and with Galectin3; co-expression with SAP18 translocates Sufu to the nucleus, while co-expression with Galectin3 translocates Galectin3 to the cytoplasm. Sufu is predominantly cytoplasmic but becomes nuclear when its putative nuclear export signal is mutated or after leptomycin B treatment. Yeast two-hybrid screen, co-immunoprecipitation, cell transfection localization assay, leptomycin B treatment The Biochemical journal Medium 14611647
2006 GSK3β is a specific binding partner of Sufu; GSK3β phosphorylates Sufu and phosphorylation-mimicking Sufu mutants show significantly decreased ability to bind Gli1 and cannot suppress Gli-mediated reporter gene expression. RNAi knockdown of GSK3β attenuates Hedgehog signaling. Mass spectrometric identification of Sufu-binding proteins, in vitro kinase assay, GST pulldown, co-immunoprecipitation, RNAi knockdown, reporter assay Biochemical and biophysical research communications High 17182001
2008 Shh signaling promotes ubiquitination of Sufu at K257, leading to its proteasomal degradation. The Sufu-K257R mutant is more stable, acts as a stronger transcription repressor, and is a more potent cell growth inhibitor. Ubiquitination assay, site-directed mutagenesis (K257R), proteasome inhibitor treatment, reporter assay, cell growth assay Oncogene High 18997815
2011 Sufu is phosphorylated at Ser-342 by GSK3β and Ser-346 by PKA; dual phosphorylation stabilizes Sufu against Shh-induced degradation. Shh signaling induces Sufu ciliary localization, which is required for turnover of phosphorylated Sufu; perturbing these phosphorylation sites alters Sufu ciliary residence time and Gli2/3 ciliary localization. Site-directed mutagenesis (S342A, S346A, phosphomimetic mutants), PKA inhibitors, primary cilia imaging, Western blot for phosphorylation The Journal of biological chemistry High 21317289
2013 Crystal structure and SAXS of full-length human SUFU and its complex with the conserved SYGHL motif of GLI reveal that GLI binding induces major conformational changes in SUFU, including rearrangement of an intrinsically disordered loop critical for pathway activation. X-ray crystallography, small-angle X-ray scattering (SAXS) Acta crystallographica. Section D, Biological crystallography High 24311597
2004 A medulloblastoma-derived truncating mutant of SUFU fails to decrease nuclear levels of β-catenin and cannot inhibit β-catenin/Tcf-mediated transcription, indicating SUFU normally exports β-catenin from the nucleus to suppress WNT signaling. Transfection of SUFU mutant, β-catenin nuclear localization assay, Tcf/LEF reporter assay Oncogene Medium 15077159
2015 Sufu binds Ci/Gli through both an N-terminal site (SIN) and a C-terminal Sufu-interacting site (SIC); SIN-binding mediates cytoplasmic sequestration of Ci/Gli, while SIC-binding is required for nuclear inhibition by masking the CBP co-activator binding site on Ci. Genetic epistasis in Drosophila, mutagenesis of SIN and SIC sites, reporter assays, co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 25941387
2014 Sufu recruits the NuRD repressor complex component p66β to block Gli-mediated Hh target gene expression in the nucleus; Mycbp (Myc-binding protein) forms an inactive complex with Gli and Sufu without Hh stimulation, but upon pathway activation Sufu/p66β dissociate from Gli, enabling Mycbp to promote Gli activity. Sufu, p66β, Mycbp, and Gli are found on Hh target gene promoters in a dynamic manner. Proteomics (Sufu interactome), chromatin immunoprecipitation, co-immunoprecipitation, zebrafish epistasis assays, cell-based reporter assays Genes & development High 25403183
2016 The F-box protein Fbxl17 targets Sufu for polyubiquitylation and proteolysis specifically in the nucleus, releasing Gli1 for Hh signal transduction; a medulloblastoma-associated Sufu mutation increases its turnover through enhanced Fbxl17-mediated polyubiquitylation. Co-immunoprecipitation, ubiquitylation assay, shRNA depletion of Fbxl17, medulloblastoma tumor growth assay, patient mutation functional analysis The EMBO journal High 27234298
2018 The E3 ubiquitin ligase Itch and β-arrestin2 form a complex that binds SuFu and induces its Lys63-linked (non-proteolytic) polyubiquitylation, which increases SuFu association with Gli3 to promote Gli3 repressor formation and keep Hh signaling off. Hh activation antagonizes this Itch-dependent polyubiquitylation of SuFu. Co-immunoprecipitation, ubiquitylation assay (K63-specific), Gli3 repressor processing assay, medulloblastoma patient mutation functional analysis Nature communications High 29515120
2014 Importin β1 (Impβ1) and SuFu bind to overlapping sites on the N-terminus of Gli1 in a mutually exclusive manner; Impβ1 mediates nuclear import of Gli1 with high nanomolar affinity, while SuFu competes with Impβ1 to prevent nuclear accumulation of Gli1, with their relative intracellular concentrations determining Gli1 localization. Quantitative live mammalian cell imaging, direct binding assay (affinity measurement), Impβ1 knockdown, competition binding assay The Biochemical journal High 24854174
2016 Nek2A phosphorylates Sufu and stabilizes it by impairing ubiquitin/proteasome degradation; phosphorylated Sufu inhibits nuclear localization and transcriptional activity of Gli2. Gli1 and Gli2 directly bind to the NEK2A gene promoter, forming a negative feedback loop in Hh signaling. Yeast two-hybrid screen, GST pulldown, co-immunoprecipitation, chromatin immunoprecipitation, reporter assay, Western blot Cellular signalling / International journal of oncology Medium 27297360 28035348
2019 PRMT7 methylates GLI2 at arginine residues R225 and R227, which are near the SUFU-binding region, and this methylation reduces GLI2-SUFU binding, thereby promoting GLI2 nuclear accumulation and Shh signaling activation. In vitro methylation assay, co-immunoprecipitation, site-directed mutagenesis, reporter assay, PRMT7-deficient MEFs Cell death and differentiation High 31000813
2017 Anti-apoptotic BCL-2 proteins (MCL-1, BCL-2, BCL-XL) that are untethered from the outer mitochondrial membrane engage a BH domain sequence in SUFU directly, promote SUFU turnover, and inhibit SUFU-GLI interaction, thereby inducing expression of GLI target genes including BCL-2, MCL-1, and BCL-XL in a feedforward loop. Co-immunoprecipitation, BH domain binding assay, BH3 mimetic pharmacological inhibition, shRNA knockdown, reporter assay Nature cell biology High 28945232
2022 ERK2 phosphorylates GLI1 at three conserved sites (S102, S116, S130) near the high-affinity SUFU binding site; multisite phosphorylation cooperates to weaken GLI1-SUFU binding affinity by over 25-fold. Phosphomimetic GLI1 variants display increased transcriptional activity in mammalian cells. In vitro kinase assay with recombinant ERK2 and GLI1, binding affinity measurements, phosphomimetic and alanine substitution mutagenesis, transcriptional reporter assay in mammalian cells Life science alliance High 35831023
2022 SUFU associates with LATS1; a deletion of residues 174-385 in SUFU disrupts SUFU-LATS1 binding and abrogates SUFU-mediated downregulation of the YAP-ACSL4 axis, increasing breast cancer cell sensitivity to ferroptosis. Co-immunoprecipitation, deletion mutagenesis, YAP activation assay, ferroptosis sensitivity assay (RSL3 treatment) iScience Medium 35800779
2023 Sufu directly interacts with TRAF6 and prevents TRAF6 oligomerization and autoubiquitination; during LPS-induced inflammation, TRAF6 undergoes liquid-liquid phase separation (condensate formation) essential for its ubiquitination and NF-κB activation, and Sufu inhibits this TRAF6 phase separation, thereby suppressing NF-κB-mediated inflammatory signaling. Co-immunoprecipitation, in vitro phase separation assay with purified proteins, FRAP, Native-PAGE, myeloid-specific Sufu knockout mice, LPS/CLP models Theranostics High 37441604
2022 SUFU binds the transcription factor ZNF281 and masks ZNF281's nuclear localization signal, causing cytoplasmic retention of ZNF281 and blocking ZNF281-promoter interactions, thereby suppressing ZNF281-driven tumor cell migration in a Hedgehog-independent manner. Co-immunoprecipitation, NLS masking assay, subcellular fractionation, ChIP on ZNF281 target promoters, in vivo tumor migration model Cell death and differentiation Medium 36220888
2017 Homozygous hypomorphic missense variants in SUFU reduce SUFU protein stability and its capacity to bind GLI3 and promote GLI3 cleavage into the repressor form GLI3R, impairing SUFU-mediated repression of the SHH pathway, resulting in Joubert syndrome with craniofacial and skeletal defects. Molecular dynamics simulation, functional studies in patient fibroblasts and cellular models (SUFU stability, GLI3 binding, GLI3R processing, Hh target gene expression) American journal of human genetics Medium 28965847
2015 Sufu regulates Gli1 protein stability by antagonizing Numb/Itch-mediated Gli1 degradation, while separately antagonizing Spop-mediated degradation of Gli2/3, demonstrating distinct mechanisms for controlling protein levels of all three Gli family members. Cell-based assays, loss-of-function in Sufu-deficient lung (in vivo), Western blot for Gli protein levels, genetic epistasis Developmental biology Medium 24886827
2006 Drosophila Su(fu) enters the nucleus in concert with Ci in response to Hh signaling; Su(fu) regulates Ci nuclear import through a mechanism dependent on the Ci nuclear localization signal, and Ci can bring Su(fu) to a multimerized Ci DNA binding site. Drosophila genetics, immunofluorescence, NLS mutant analysis, DNA binding site assay Developmental biology Medium 16595130
2012 Kif7 plays a role in the turnover of Sufu and exclusion of Sufu-Gli complexes from the primary cilium in chondrocytes; halving the dose of Sufu restores normal hedgehog pathway activity in Kif7-null mice, demonstrating that Kif7's positive role in Hh signaling is to restrict the inhibitory activity of Sufu. Mouse genetic epistasis (Kif7-null with Sufu heterozygous rescue), primary cilia immunofluorescence, Western blot Development (Cambridge, England) High 21795282
2015 SUFU suppresses graft-versus-host disease by downregulating HLA-DR expression on dendritic cells; ectopic SUFU expression reduces surface HLA-DR and suppresses allogeneic mixed leukocyte response, while SUFU silencing enhances HLA-DR expression and increases MLR. Ectopic expression and siRNA silencing in THP-1-derived dendritic cells, HLA-DR surface staining, mixed leukocyte reaction assay Scientific reports Medium 26067905

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Mutations in SUFU predispose to medulloblastoma. Nature genetics 608 12068298
2007 MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proceedings of the National Academy of Sciences of the United States of America 450 18077375
2010 A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes. The Journal of cell biology 319 20956384
2005 Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas. The British journal of dermatology 313 15656799
2009 Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes & development 299 19684112
2014 Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 214 25403219
2006 Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development. The Journal of pathology 187 16294371
2002 Characterization of the physical interaction of Gli proteins with SUFU proteins. The Journal of biological chemistry 147 12426310
2009 Identification of a SUFU germline mutation in a family with Gorlin syndrome. American journal of medical genetics. Part A 139 19533801
2018 Exosomal miR-423-5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer. Molecular carcinogenesis 125 29749061
2012 Loss of SUFU function in familial multiple meningioma. American journal of human genetics 123 22958902
2019 lncRNA GAS5-promoted apoptosis in triple-negative breast cancer by targeting miR-378a-5p/SUFU signaling. Journal of cellular biochemistry 98 31692053
2012 The ciliary Evc/Evc2 complex interacts with Smo and controls Hedgehog pathway activity in chondrocytes by regulating Sufu/Gli3 dissociation and Gli3 trafficking in primary cilia. Human molecular genetics 93 23026747
2004 The negative regulator of Gli, Suppressor of fused (Sufu), interacts with SAP18, Galectin3 and other nuclear proteins. The Biochemical journal 93 14611647
2011 Dual Phosphorylation of suppressor of fused (Sufu) by PKA and GSK3beta regulates its stability and localization in the primary cilium. The Journal of biological chemistry 92 21317289
2012 High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 90 22508808
2010 SufU is an essential iron-sulfur cluster scaffold protein in Bacillus subtilis. Journal of bacteriology 81 20097860
2009 Sufu recruits GSK3beta for efficient processing of Gli3. Biochemical and biophysical research communications 81 19622347
2018 MicroRNA-214 promotes hepatic stellate cell activation and liver fibrosis by suppressing Sufu expression. Cell death & disease 79 29915227
2008 Hedgehog signaling promotes the degradation of tumor suppressor Sufu through the ubiquitin-proteasome pathway. Oncogene 69 18997815
2016 MiRNA-194 activates the Wnt/β-catenin signaling pathway in gastric cancer by targeting the negative Wnt regulator, SUFU. Cancer letters 67 27810403
2013 Fe-S cluster biogenesis in Gram-positive bacteria: SufU is a zinc-dependent sulfur transfer protein. Biochemistry 64 24321018
2015 Multisite interaction with Sufu regulates Ci/Gli activity through distinct mechanisms in Hh signal transduction. Proceedings of the National Academy of Sciences of the United States of America 63 25941387
2021 Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu). Stem cell research & therapy 62 34099038
2012 Kif7 regulates Gli2 through Sufu-dependent and -independent functions during skin development and tumorigenesis. Development (Cambridge, England) 62 23034632
2004 Failure of a medulloblastoma-derived mutant of SUFU to suppress WNT signaling. Oncogene 61 15077159
2016 SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and medulloblastoma development. The EMBO journal 57 27234298
2013 Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation. Acta crystallographica. Section D, Biological crystallography 57 24311597
2012 Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation. Familial cancer 57 22829011
2011 Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and SUFU mutations to sporadic medulloblastoma. Familial cancer 53 21188540
2019 Exosomal miR-423-5p mediates the proangiogenic activity of human adipose-derived stem cells by targeting Sufu. Stem cell research & therapy 52 30898155
2018 Itch/β-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis. Nature communications 52 29515120
2016 Multiple Hereditary Infundibulocystic Basal Cell Carcinoma Syndrome Associated With a Germline SUFU Mutation. JAMA dermatology 48 26677003
2017 Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects. American journal of human genetics 47 28965847
2011 Kif7 promotes hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu. Development (Cambridge, England) 47 21795282
2006 GSK3beta positively regulates Hedgehog signaling through Sufu in mammalian cells. Biochemical and biophysical research communications 47 17182001
2022 SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway. iScience 46 35800779
2015 microRNA-214 promotes epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting the suppressor-of-fused protein (Sufu). Oncotarget 46 26462018
2008 Role and regulation of human tumor suppressor SUFU in Hedgehog signaling. Advances in cancer research 46 19055941
2009 Structural studies of the Enterococcus faecalis SufU [Fe-S] cluster protein. BMC biochemistry 45 19187533
2009 Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations. Journal of medical genetics 43 19833601
2021 Periodontitis-compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA-378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling. Cell proliferation 41 33759282
2017 Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor. Nature cell biology 41 28945232
2014 Regulation of Sufu activity by p66β and Mycbp provides new insight into vertebrate Hedgehog signaling. Genes & development 39 25403183
2016 Crosstalk between the vitamin D receptor (VDR) and miR-214 in regulating SuFu, a hedgehog pathway inhibitor in breast cancer cells. Experimental cell research 35 27693451
2017 Zinc-Ligand Swapping Mediated Complex Formation and Sulfur Transfer between SufS and SufU for Iron-Sulfur Cluster Biogenesis in Bacillus subtilis. Journal of the American Chemical Society 34 29235855
2006 Regulation of Ci and Su(fu) nuclear import in Drosophila. Developmental biology 34 16595130
2019 LIFR-AS1 modulates Sufu to inhibit cell proliferation and migration by miR-197-3p in breast cancer. Bioscience reports 33 31127025
2019 Sufu- and Spop-mediated downregulation of Hedgehog signaling promotes beta cell differentiation through organ-specific niche signals. Nature communications 33 31604927
2019 GLI2 Modulated by SUFU and SPOP Induces Intestinal Stem Cell Niche Signals in Development and Tumorigenesis. Cell reports 31 31167144
2011 Volatile components of the enzyme-ripened sufu, a Chinese traditional fermented product of soy bean. Journal of bioscience and bioengineering 30 22051578
2021 SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum. Journal of medical genetics 28 34675124
2011 Mechanistic characterization of sulfur transfer from cysteine desulfurase SufS to the iron-sulfur scaffold SufU in Bacillus subtilis. FEBS letters 28 21236255
2023 Sufu limits sepsis-induced lung inflammation via regulating phase separation of TRAF6. Theranostics 27 37441604
2018 Mutations in SUFU and PTCH1 genes may cause different cutaneous cancer predisposition syndromes: similar, but not the same. Familial cancer 27 29356994
2019 PRMT7 methylates and suppresses GLI2 binding to SUFU thereby promoting its activation. Cell death and differentiation 25 31000813
2023 Structural and Biochemical Characterization of Mycobacterium tuberculosis Zinc SufU-SufS Complex. Biomolecules 24 37238602
2021 Metagenomic insights into the bacteria responsible for producing biogenic amines in sufu. Food microbiology 24 33875200
2016 Crystal Structure of Bacillus subtilis Cysteine Desulfurase SufS and Its Dynamic Interaction with Frataxin and Scaffold Protein SufU. PloS one 24 27382962
2011 Enterococcus faecalis SufU scaffold protein enhances SufS desulfurase activity by acquiring sulfur from its cysteine-153. Biochimica et biophysica acta 22 21835272
2010 Some biochemical and physical changes during the preparation of the enzyme-ripening sufu, a fermented product of soybean curd. Journal of agricultural and food chemistry 22 20218723
2021 Dual activation of Hedgehog and Wnt/β-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer. Aging 21 33848981
2019 Mesenchymal Sufu Regulates Development of Mandibular Molars via Shh Signaling. Journal of dental research 21 31499014
2018 Effective anti-programmed death-1 therapy in a SUFU-mutated patient with Gorlin-Goltz syndrome. The British journal of dermatology 21 29603722
2017 miR-342-3p elevates osteogenic differentiation of umbilical cord mesenchymal stem cells via inhibiting Sufu in vitro. Biochemical and biophysical research communications 21 28765042
2020 High-Throughput Sequencing and Metabolomics Reveal Differences in Bacterial Diversity and Metabolites Between Red and White Sufu. Frontiers in microbiology 20 32390991
2017 Reduction of biogenic amines in sufu by ethanol addition during ripening stage. Food chemistry 20 28873546
2014 Differential regulation of Gli proteins by Sufu in the lung affects PDGF signaling and myofibroblast development. Developmental biology 20 24886827
2014 Overlapping binding sites for importin β1 and suppressor of fused (SuFu) on glioma-associated oncogene homologue 1 (Gli1) regulate its nuclear localization. The Biochemical journal 19 24854174
2021 Positive feedback of SuFu negating protein 1 on Hedgehog signaling promotes colorectal tumor growth. Cell death & disease 18 33608498
2021 MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT. Heliyon 18 33912703
2018 miR-423-5p inhibits myoblast proliferation and differentiation by targeting Sufu. Journal of cellular biochemistry 18 29923621
2018 MicroRNA-874 targeting SUFU involves in osteoblast proliferation and differentiation in osteoporosis rats through the Hedgehog signaling pathway. Biochemical and biophysical research communications 18 30342851
2025 Effects of Cold Post-Fermentation Process on Microbial Diversity and Biogenic Amines in Protease-Assisted Fermented sufu. Foods (Basel, Switzerland) 17 40077437
2020 Heterozygous truncating variants in SUFU cause congenital ocular motor apraxia. Genetics in medicine : official journal of the American College of Medical Genetics 17 33024317
2016 Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway. International journal of oncology 17 28035348
2012 Antagonistic and cooperative actions of Kif7 and Sufu define graded intracellular Gli activities in Hedgehog signaling. PloS one 17 23166838
2004 No evidence for mutations or altered expression of the Suppressor of Fused gene (SUFU) in primitive neuroectodermal tumours. Neuropathology and applied neurobiology 17 15488029
2000 Genomic organization, chromosomal assignment, and expression analysis of the mouse suppressor of fused gene (Sufu) coding a Gli protein partner. Mammalian genome : official journal of the International Mammalian Genome Society 17 10920228
2022 ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1. Life science alliance 16 35831023
2020 miR-214-3p-Sufu-GLI1 is a novel regulatory axis controlling inflammatory smooth muscle cell differentiation from stem cells and neointimal hyperplasia. Stem cell research & therapy 16 33143723
2017 Nomegestrol Acetate Suppresses Human Endometrial Cancer RL95-2 Cells Proliferation In Vitro and In Vivo Possibly Related to Upregulating Expression of SUFU and Wnt7a. International journal of molecular sciences 16 28640224
2016 Nek2A phosphorylates and stabilizes SuFu: A new strategy of Gli2/Hedgehog signaling regulatory mechanism. Cellular signalling 16 27297360
2015 Multiple skin hamartomata: a possible novel clinical presentation of SUFU neoplasia syndrome. Familial cancer 16 25287320
2013 RIO kinase 3 acts as a SUFU-dependent positive regulator of Hedgehog signaling. Cellular signalling 16 24018050
2011 Fermentation temperature affects the antioxidant activity of the enzyme-ripened sufu, an oriental traditional fermented product of soybean. Journal of bioscience and bioengineering 16 21497549
2004 Mucoraceous moulds involved in the commercial fermentation of Sufu Pehtze. Antonie van Leeuwenhoek 16 15028872
2022 Inhibition of the transcription factor ZNF281 by SUFU to suppress tumor cell migration. Cell death and differentiation 15 36220888
2015 Sufu and Kif7 in limb patterning and development. Developmental dynamics : an official publication of the American Association of Anatomists 15 25581370
2022 Sufu- and Spop-mediated regulation of Gli2 is essential for the control of mammalian cochlear hair cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 14 36252002
2021 Microbial Community Succession and Metabolite Changes During Fermentation of BS Sufu, the Fermented Black Soybean Curd by Rhizopus microsporus, Rhizopus oryzae, and Actinomucor elegans. Frontiers in microbiology 14 34248874
2020 SUFU mediates EMT and Wnt/β-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer. Cell cycle (Georgetown, Tex.) 14 33017570
2012 Suppressor of fused (Sufu) mediates the effect of parathyroid hormone-like hormone (Pthlh) on chondrocyte differentiation in the growth plate. The Journal of biological chemistry 14 22930757
2021 Comparative analysis of the microbial community and nutritional quality of sufu. Food science & nutrition 13 34401063
2019 Effects of miRNA-342-3p in modulating Hedgehog signaling pathway of human umbilical cord mesenchymal stem cells by down-regulating Sufu. Oral diseases 13 30790389
2018 Itraconazole perturbs colorectal cancer dormancy through SUFU-mediated WNT inhibition. Molecular & cellular oncology 13 30250932
2015 A Comparison of Ci/Gli Activity as Regulated by Sufu in Drosophila and Mammalian Hedgehog Response. PloS one 13 26271100
2022 Dynamic correlations between major enzymatic activities, physicochemical properties and targeted volatile compounds in naturally fermented plain sufu during production. Food chemistry 12 35078100
2017 Down-regulation of microRNA-224 -inhibites growth and epithelial-to-mesenchymal transition phenotype -via modulating SUFU expression in bladder cancer cells. International journal of biological macromolecules 12 28780419
2015 Genome-wide single-nucleotide polymorphism analysis revealed SUFU suppression of acute graft-versus-host disease through downregulation of HLA-DR expression in recipient dendritic cells. Scientific reports 12 26067905