Gene Symbol: Sufu
Description: SUFU negative regulator of hedgehog signaling
Alias: Su(fu), suppressor of fused homolog
Species: mouse
Products:     Sufu

Top Publications

  1. Pearse R, Collier L, Scott M, Tabin C. Vertebrate homologs of Drosophila suppressor of fused interact with the gli family of transcriptional regulators. Dev Biol. 1999;212:323-36 pubmed
    ..This interaction may be significant for transcriptional regulation, as recombinant Su(fu) enhances the ability of Gli proteins to bind DNA in electrophoretic mobility shift assays. ..
  2. Liu J, Heydeck W, Zeng H, Liu A. Dual function of suppressor of fused in Hh pathway activation and mouse spinal cord patterning. Dev Biol. 2012;362:141-53 pubmed publisher
    ..Suppressor of Fused (Sufu), a Gli-interacting protein, modulates the D/V patterning of the spinal cord by antagonizing Hh signaling...
  3. Jia J, Kolterud A, Zeng H, Hoover A, Teglund S, Toftgard R, et al. Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia. Dev Biol. 2009;330:452-60 pubmed publisher
    ..In the current study, we demonstrate that mouse Suppressor of Fused (Sufu) interacts with Gli proteins and inhibits Gli activator activity in the absence of cilia...
  4. Haycraft C, Banizs B, Aydin Son Y, Zhang Q, Michaud E, Yoder B. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet. 2005;1:e53 pubmed
    ..Thus, our data support a model where cilia have a direct role in Gli processing and Shh signal transduction. ..
  5. Cheng S, Bishop J. Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex. Proc Natl Acad Sci U S A. 2002;99:5442-7 pubmed
    ..These results provide biochemical evidence that Su(fu) directly participates in modulating the transcriptional activity of Gli. ..
  6. Yue S, Chen Y, Cheng S. Hedgehog signaling promotes the degradation of tumor suppressor Sufu through the ubiquitin-proteasome pathway. Oncogene. 2009;28:492-9 pubmed publisher
    ..Mutational inactivation of Shh receptor Patched (Ptch) and a downstream gene Suppressor of fused (Sufu), both of which are negative regulators of the pathway, increases susceptibility to cerebellum cancer in humans and ..
  7. Szczepny A, Hime G, Loveland K. Expression of hedgehog signalling components in adult mouse testis. Dev Dyn. 2006;235:3063-70 pubmed
    ..In contrast, mRNA encoding SuFu, a negative regulator of Hh signalling, was most predominant in round spermatids and the protein is evident in ..
  8. Kise Y, Morinaka A, Teglund S, Miki H. Sufu recruits GSK3beta for efficient processing of Gli3. Biochem Biophys Res Commun. 2009;387:569-74 pubmed publisher
    ..Hh) signaling activates the transcription factor Gli by suppressing the function of the suppressor of fused (Sufu) protein in mammals...
  9. Wang C, Pan Y, Wang B. Suppressor of fused and Spop regulate the stability, processing and function of Gli2 and Gli3 full-length activators but not their repressors. Development. 2010;137:2001-9 pubmed publisher
    ..In this study, we show that loss of suppressor of fused (Sufu; an inhibitory effector for Gli proteins) results in destabilization of Gli2 and Gli3 full-length activators but ..

More Information


  1. Humke E, Dorn K, Milenkovic L, Scott M, Rohatgi R. The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins. Genes Dev. 2010;24:670-82 pubmed publisher
    ..We show that the interaction between Gli3 and Suppressor of Fused (Sufu) regulates the formation of either repressor or activator forms of Gli3...
  2. Chen M, Wilson C, Li Y, Law K, Lu C, Gacayan R, et al. Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes Dev. 2009;23:1910-28 pubmed publisher
    ..We focus on Suppressor of fused (Sufu), a major Hh regulator in mammals, and reveal that Sufu controls protein levels of full-length Gli transcription ..
  3. Endoh Yamagami S, Evangelista M, Wilson D, Wen X, Theunissen J, Phamluong K, et al. The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development. Curr Biol. 2009;19:1320-6 pubmed publisher
    ..These results suggest a role for Kif7 in coordinating Hh signal transduction at the tip of cilia and preventing Gli3 cleavage into a repressor form in the presence of Hh. ..
  4. Tukachinsky H, Lopez L, Salic A. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes. J Cell Biol. 2010;191:415-28 pubmed publisher
    ..In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu...
  5. Meng X, Poon R, Zhang X, Cheah A, Ding Q, Hui C, et al. Suppressor of fused negatively regulates beta-catenin signaling. J Biol Chem. 2001;276:40113-9 pubmed
    ..These observations indicate that Su(fu) negatively regulates beta-catenin signaling and that CRM-1-mediated nuclear export plays a role in this regulation. Our results also suggest that Su(fu) acts as a tumor suppressor. ..
  6. Grimm T, Teglund S, Tackels D, Sangiorgi E, Gurrieri F, Schwartz C, et al. Genomic organization and embryonic expression of Suppressor of Fused, a candidate gene for the split-hand/split-foot malformation type 3. FEBS Lett. 2001;505:13-7 pubmed
    ..SU(FU) was considered a candidate gene for the split-hand/split-foot malformation type 3 (SHFM3). However, no alterations in the SU(FU) gene were found in SHFM3 patients. ..
  7. Barnfield P, Zhang X, Thanabalasingham V, Yoshida M, Hui C. Negative regulation of Gli1 and Gli2 activator function by Suppressor of fused through multiple mechanisms. Differentiation. 2005;73:397-405 pubmed
    ..Together, these observations reveal that Su(fu) regulates the activity of Gli1 and Gli2 through distinct cytoplasmic and nuclear mechanisms. ..
  8. Law K, Makino S, Mo R, Zhang X, Puviindran V, Hui C. Antagonistic and cooperative actions of Kif7 and Sufu define graded intracellular Gli activities in Hedgehog signaling. PLoS ONE. 2012;7:e50193 pubmed publisher
    ..It remains unclear how distinct intracellular Gli activity is generated. Here, we demonstrate that Sufu acts universally as a negative regulator of Hh signaling, whereas Kif7 inhibits Gli activity in cooperation with, ..
  9. Varjosalo M, Li S, Taipale J. Divergence of hedgehog signal transduction mechanism between Drosophila and mammals. Dev Cell. 2006;10:177-86 pubmed
  10. Cooper A, Yu K, Brueckner M, Brailey L, Johnson L, McGrath J, et al. Cardiac and CNS defects in a mouse with targeted disruption of suppressor of fused. Development. 2005;132:4407-17 pubmed
    ..Targeted disruption of the murine suppressor of fused gene (Sufu) led to a phenotype that included neural tube defects and lethality at mid-gestation (9.0-10.5 dpc)...
  11. Hsu S, Zhang X, Yu C, Li Z, Wunder J, Hui C, et al. Kif7 promotes hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu. Development. 2011;138:3791-801 pubmed publisher
    ..Here, we show that Suppressor of fused (Sufu) and Kif7 are essential regulators of Ihh signaling...
  12. Ocbina P, Anderson K. Intraflagellar transport, cilia, and mammalian Hedgehog signaling: analysis in mouse embryonic fibroblasts. Dev Dyn. 2008;237:2030-8 pubmed publisher
    ..Similarly, decreased activity of either Sufu or PKA, two negative regulators of Hh signal transduction, activates the pathway in wild-type, but not IFT mutant, ..
  13. Lee Y, Kawagoe R, Sasai K, Li Y, Russell H, Curran T, et al. Loss of suppressor-of-fused function promotes tumorigenesis. Oncogene. 2007;26:6442-7 pubmed
    ..Here, we report that loss of a regulator of the SHH pathway, Suppressor of Fused (Sufu), resulted in early embryonic lethality in the mouse similar to inactivation of another SHH regulator, Patched1 (..
  14. Svärd J, Heby Henricson K, Henricson K, Persson Lek M, Rozell B, Lauth M, et al. Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway. Dev Cell. 2006;10:187-97 pubmed
    ..Here, we show that ablation of the mouse Suppressor of fused (Sufu), an intracellular pathway component, leads to embryonic lethality at approximately E9...
  15. Zhulyn O, Li D, Deimling S, Vakili N, Mo R, Puviindran V, et al. A switch from low to high Shh activity regulates establishment of limb progenitors and signaling centers. Dev Cell. 2014;29:241-9 pubmed publisher
  16. Pospisilik J, Schramek D, Schnidar H, Cronin S, Nehme N, Zhang X, et al. Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate. Cell. 2010;140:148-60 pubmed publisher
    ..These findings identify a role for hedgehog signaling in white/brown adipocyte determination and link in vivo RNAi-based scanning of the Drosophila genome to regulation of adipocyte cell fate in mammals. ..
  17. Simon Chazottes D, Paces Fessy M, Lamour Isnard C, Guenet J, Blanchet Tournier M. Genomic organization, chromosomal assignment, and expression analysis of the mouse suppressor of fused gene (Sufu) coding a Gli protein partner. Mamm Genome. 2000;11:614-21 pubmed
    Suppressor of fused (Sufu) is a negative regulator of the Hedgehog pathway both in Drosophila and vertebrates. Here, we report the genomic organization of the mouse Sufu gene (mSufu)...
  18. Stone D, Murone M, Luoh S, Ye W, Armanini M, Gurney A, et al. Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli. J Cell Sci. 1999;112 ( Pt 23):4437-48 pubmed
    ..The data further suggest that Su(fu) can act by binding to Gli and inhibiting Gli-mediated transactivation as well as by serving as an adaptor protein, which links Gli to the Slimb-dependent proteasomal degradation pathway. ..
  19. Ding Q, Fukami S, Meng X, Nishizaki Y, Zhang X, Sasaki H, et al. Mouse suppressor of fused is a negative regulator of sonic hedgehog signaling and alters the subcellular distribution of Gli1. Curr Biol. 1999;9:1119-22 pubmed
    ..Our findings indicate that mSu(fu) can function as a negative regulator of Shh signaling and suggest that this effect is mediated by interaction with Gli transcription factors. ..
  20. Li J, Wang Q, Cui Y, Yang X, Li Y, Zhang X, et al. Suppressor of Fused Is Required for Determining Digit Number and Identity via Gli3/Fgfs/Gremlin. PLoS ONE. 2015;10:e0128006 pubmed publisher
    ..Suppressor of Fused (Sufu), an intracellular negative regulator of Shh signaling via Gli2 and Gli3, is implicated in early development of the ..
  21. Caparrós Martín J, Valencia M, Reytor E, Pacheco M, Fernandez M, Perez Aytes A, et al. 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. Hum Mol Genet. 2013;22:124-39 pubmed publisher
    ..However, Gli3 recruitment to cilia tips was reduced and Sufu/Gli3 dissociation was impaired...
  22. Aavikko M, Li S, Saarinen S, Alhopuro P, Kaasinen E, Morgunova E, et al. Loss of SUFU function in familial multiple meningioma. Am J Hum Genet. 2012;91:520-6 pubmed publisher
    ..We combined genome-wide linkage analysis and exome sequencing, and we identified in suppressor of fused homolog (Drosophila), SUFU, a c.367C>T (p.Arg123Cys) mutation segregating with the meningiomas in the family...
  23. Kim J, Gill P, Rotin L, van Eede M, Henkelman R, Hui C, et al. Suppressor of fused controls mid-hindbrain patterning and cerebellar morphogenesis via GLI3 repressor. J Neurosci. 2011;31:1825-36 pubmed publisher cerebellar patterning and cell differentiation by generating mice with targeted deletion of Suppressor of Fused (SuFu), a regulator of Sonic Hedgehog signaling, in the mid-hindbrain...
  24. Hillman R, Feng B, Ni J, Woo W, Milenkovic L, Hayden Gephart M, et al. Neuropilins are positive regulators of Hedgehog signal transduction. Genes Dev. 2011;25:2333-46 pubmed publisher
    ..mediate Hh transduction between activated Smoothened (Smo) protein and the negative regulator Suppressor of Fused (SuFu)...
  25. Lin C, Yao E, Wang K, Nozawa Y, Shimizu H, Johnson J, et al. Regulation of Sufu activity by p66β and Mycbp provides new insight into vertebrate Hedgehog signaling. Genes Dev. 2014;28:2547-63 pubmed publisher
    Control of Gli function by Suppressor of Fused (Sufu), a major negative regulator, is a key step in mammalian Hedgehog (Hh) signaling, but how this is achieved in the nucleus is unknown...
  26. Makino S, Zhulyn O, Mo R, Puviindran V, Zhang X, Murata T, et al. T396I mutation of mouse Sufu reduces the stability and activity of Gli3 repressor. PLoS ONE. 2015;10:e0119455 pubmed publisher
    ..Recent studies using a Sufu knockout mouse have indicated that Sufu is involved in regulating Gli2 and Gli3 activator and repressor activity at ..
  27. Wu X, Zhang L, Toombs J, Kuo Y, Piazza J, Tuladhar R, et al. Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor. Nat Cell Biol. 2017;19:1226-1236 pubmed publisher
    ..Anti-apoptotic BCL-2 proteins engage a BCL-2 homology (BH) domain sequence found in SUFU (suppressor of fused), a tumour suppressor and antagonist of the GLI DNA-binding proteins...
  28. Zeruth G, Yang X, Jetten A. Modulation of the transactivation function and stability of Krüppel-like zinc finger protein Gli-similar 3 (Glis3) by Suppressor of Fused. J Biol Chem. 2011;286:22077-89 pubmed publisher
    ..We demonstrated that Glis3 interacts with Suppressor of Fused (SUFU), which involves a VYGHF motif located within this conserved region...
  29. Delattre M, Briand S, Paces Fessy M, Blanchet Tournier M. The Suppressor of fused gene, involved in Hedgehog signal transduction in Drosophila, is conserved in mammals. Dev Genes Evol. 1999;209:294-300 pubmed
    ..These data are discussed in the light of their evolutionary relationships. ..
  30. Ruel L, Therond P. Variations in Hedgehog signaling: divergence and perpetuation in Sufu regulation of Gli. Genes Dev. 2009;23:1843-8 pubmed publisher
    ..1910-1928) demonstrate that mouse Suppressor of fused (Sufu) regulates the stability of the transcription factors Gli2 and Gli3 by antagonizing the conserved Gli degradation ..
  31. Cwinn M, Mazerolle C, McNeill B, Ringuette R, Thurig S, Hui C, et al. Suppressor of fused is required to maintain the multipotency of neural progenitor cells in the retina. J Neurosci. 2011;31:5169-80 pubmed publisher
    ..Suppressor of fused (Sufu) has been recently identified as a critical regulator of Hh signaling in mammals...
  32. Chang C, Chang Y, Millington G, Brugmann S. Craniofacial Ciliopathies Reveal Specific Requirements for GLI Proteins during Development of the Facial Midline. PLoS Genet. 2016;12:e1006351 pubmed publisher
    ..Furthermore, these studies suggest a novel role for GLI2R in craniofacial development. ..
  33. Patterson V, Damrau C, Paudyal A, Reeve B, Grimes D, Stewart M, et al. Mouse hitchhiker mutants have spina bifida, dorso-ventral patterning defects and polydactyly: identification of Tulp3 as a novel negative regulator of the Sonic hedgehog pathway. Hum Mol Genet. 2009;18:1719-39 pubmed publisher
    ..of Gli3, and we demonstrate that transcriptional regulation of other negative regulators (Rab23, Fkbp8, Thm1, Sufu and PKA) is not affected...
  34. Tostar U, Finta C, Rahman M, Shimokawa T, Zaphiropoulos P. Novel mechanism of action on Hedgehog signaling by a suppressor of fused carboxy terminal variant. PLoS ONE. 2012;7:e37761 pubmed publisher
    The Suppressor of Fused (SUFU) protein plays an essential role in the Hedgehog (HH) signaling pathway, by regulation of the GLI transcription factors...
  35. Pozniak C, Langseth A, Dijkgraaf G, Choe Y, Werb Z, Pleasure S. Sox10 directs neural stem cells toward the oligodendrocyte lineage by decreasing Suppressor of Fused expression. Proc Natl Acad Sci U S A. 2010;107:21795-800 pubmed publisher
    ..We performed a chromatin immunoprecipitation-based bioinformatic screen and identified Suppressor of Fused (Sufu) as a direct target of repression by Sox10...
  36. Hoelzl M, Heby Henricson K, Gerling M, Dias J, Kuiper R, Trünkle C, et al. Differential requirement of SUFU in tissue development discovered in a hypomorphic mouse model. Dev Biol. 2017;429:132-146 pubmed publisher
    Suppressor of Fused (SUFU) is an essential negative regulator of the Hedgehog (HH) pathway and involved in GLI transcription factor regulation...
  37. Zhulyn O, Hui C. Sufu and Kif7 in limb patterning and development. Dev Dyn. 2015;244:468-78 pubmed publisher
    ..Gli1, 2 and 3 are dynamically expressed during patterning. Downstream of Shh, their activity is regulated by Sufu and Kif7, core components of the Shh signaling cascade...
  38. Kucerova R, Dorà N, Mort R, Wallace K, Leiper L, Lowes C, et al. Interaction between hedgehog signalling and PAX6 dosage mediates maintenance and regeneration of the corneal epithelium. Mol Vis. 2012;18:139-50 pubmed
  39. Szczepny A, Wagstaff K, Dias M, Gajewska K, Wang C, Davies R, et al. Overlapping binding sites for importin ?1 and suppressor of fused (SuFu) on glioma-associated oncogene homologue 1 (Gli1) regulate its nuclear localization. Biochem J. 2014;461:469-76 pubmed publisher
    ..may be regulated by interaction with other cellular factors, such as the negative regulator suppressor of fused (SuFu)...
  40. Chari N, Romano R, Koster M, Jaks V, Roop D, Flores E, et al. Interaction between the TP63 and SHH pathways is an important determinant of epidermal homeostasis. Cell Death Differ. 2013;20:1080-8 pubmed publisher
    ..An upregulation of suppressor of fused (SUFU), a negative regulator of the HH pathway, lowered HH pathway activity and was accompanied by loss of BCL2 ..
  41. Huse J, Holland E. Genetically engineered mouse models of brain cancer and the promise of preclinical testing. Brain Pathol. 2009;19:132-43 pubmed publisher
    ..Examples showcasing the use of GEMMs in the testing of molecularly targeted therapeutics are given, and relevant topics, such as stem cell biology, in vivo imaging technology and radiotherapy, are also addressed. ..
  42. Svärd J, Rozell B, Toftgard R, Teglund S. Tumor suppressor gene co-operativity in compound Patched1 and suppressor of fused heterozygous mutant mice. Mol Carcinog. 2009;48:408-19 pubmed publisher
    ..Patched1 (Ptch1) and Suppressor of fused (Sufu) are two essential negative regulators of the pathway with tumor suppressor activity...
  43. Takenaka K, Kise Y, Miki H. GSK3beta positively regulates Hedgehog signaling through Sufu in mammalian cells. Biochem Biophys Res Commun. 2007;353:501-8 pubmed
    ..pathway is ultimately transmitted by the zinc-finger transcriptional factor Gli, of which activity is suppressed by Sufu, a negative regulator of this signaling...
  44. Li B, Rauhauser A, Dai J, Sakthivel R, Igarashi P, Jetten A, et al. Increased hedgehog signaling in postnatal kidney results in aberrant activation of nephron developmental programs. Hum Mol Genet. 2011;20:4155-66 pubmed publisher
    ..This is the first description of a molecular mechanism that links the Hh signaling pathway to cystic kidney diseases and can open new avenues for the treatment of diverse ciliopathies. ..
  45. Chen Y, Yue S, Xie L, Pu X, Jin T, Cheng S. Dual Phosphorylation of suppressor of fused (Sufu) by PKA and GSK3beta regulates its stability and localization in the primary cilium. J Biol Chem. 2011;286:13502-11 pubmed publisher
    Suppressor of fused (Sufu) is an essential negative regulator of the sonic hedgehog (Shh) pathway, but little is known about how Sufu itself is normally regulated...
  46. Raducu M, Fung E, Serres S, Infante P, Barberis A, Fischer R, et al. SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and medulloblastoma development. EMBO J. 2016;35:1400-16 pubmed publisher
    ..b>Sufu (Suppressor of fused) is a central regulator of Hh (Hedgehog) signaling and acts as a tumor suppressor by ..
  47. Yabut O, Fernandez G, Huynh T, Yoon K, Pleasure S. Suppressor of Fused Is Critical for Maintenance of Neuronal Progenitor Identity during Corticogenesis. Cell Rep. 2015;12:2021-34 pubmed publisher
    ..Here, we show that Suppressor of Fused (Sufu) controls PN specification by maintaining the identity of NPCs in the embryonic neocortex...
  48. Jagani Z, Mora Blanco E, Sansam C, McKenna E, Wilson B, Chen D, et al. Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway. Nat Med. 2010;16:1429-33 pubmed publisher
    ..Therefore, our studies reveal that SNF5 is a key mediator of Hh signaling and that aberrant activation of GLI1 is a previously undescribed targetable mechanism contributing to the growth of MRT cells. ..
  49. Liu J, Zeng H, Liu A. The loss of Hh responsiveness by a non-ciliary Gli2 variant. Development. 2015;142:1651-60 pubmed publisher
    ..Finally, Gli2(ΔCLR) exhibits strong transcriptional activator activity in the absence of Sufu, suggesting that the lack of its activation in vivo results from a specific failure in relieving the inhibitory ..
  50. Lin C, Chen M, Yao E, Song H, Gacayan R, Hui C, et al. Differential regulation of Gli proteins by Sufu in the lung affects PDGF signaling and myofibroblast development. Dev Biol. 2014;392:324-33 pubmed publisher
    ..This process is controlled in part by a major negative regulator, Sufu, through its effects on Gli protein level, distribution and activity...
  51. Zeng H, Jia J, Liu A. Coordinated translocation of mammalian Gli proteins and suppressor of fused to the primary cilium. PLoS ONE. 2010;5:e15900 pubmed publisher
    ..Hh signaling effectors, the Gli family of transcription factors, and their negative regulator, Suppressor of Fused (Sufu), accumulate at the tips of cilia; however, the molecular mechanism regulating this localization remains elusive...
  52. Cai H, Liu A. Spop regulates Gli3 activity and Shh signaling in dorsoventral patterning of the mouse spinal cord. Dev Biol. 2017;432:72-85 pubmed publisher
    ..loss of Spop restores the maximal Shh pathway activation and ventral cell fate specification in the Gli1;Sufu double mutant spinal cord...
  53. Hsu S, Zhang X, Cheng S, Wunder J, Hui C, Alman B. Suppressor of fused (Sufu) mediates the effect of parathyroid hormone-like hormone (Pthlh) on chondrocyte differentiation in the growth plate. J Biol Chem. 2012;287:36222-8 pubmed publisher
    ..In mice lacking the Hh mediator Suppressor of fused (Sufu), Pthlh treatment resulted in the up-regulation of Hh activity and an increased number of hypertrophic chondrocytes...