GLI proteins bind SUFU

Stable Identifier
R-HSA-5610723
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Vertebrate SUFU plays a critical role in the negative regulation of Hh signaling in the absence of ligand. Disruption of SUFU causes constitutive activation of the pathway, and is associated with the development of medulloblastoma in humans (Cooper et al, 2005; Svard et al, 2006; Taylor et al, 2002; Pastorino et al, 2009). SUFU binds directly to all three GLI proteins (Pearse et al, 1999; Stone et al, 1999; Jia et al, 2009; Svard et al, 2006). Formation of a SUFU:GLI complex is required for the processing of GLI3 to the GLI3R repressor form, and the processing depends on transit through the primary cilia (Kise et al, 2009; Humke et al, 2010; Huangfu and Anderson, 2005). Despite this, primary cilia are not required for SUFU to inhibit GLI activity; SUFU may also serve in a cilia-independent manner to sequester the full-length protein in the cytoplasm in the absence of Hh signal (Chen et al, 2009; Humke et al, 2010; Jia et al, 2009; Tukachinsky et al, 2010). After processing, GLI3R dissociates from SUFU and its activity is SUFU-independent (Humke et al, 2010; Tukachinsky et al, 2010). Nuclear SUFU may also play a direct role as a transcriptional co-repressor through interaction with the N-terminal DNA-binding domain of GLI proteins, though this remains to be fully elaborated (Monnier et al, 1998; Pearse et al, 1999; Cheng and Bishop, 2002; Paces-Fessy et al, 2004; Dunaeva et al, 2003; Szczepny et al, 2014).

Literature References
PubMed ID Title Journal Year
24854174 Overlapping binding sites for importin ?1 and suppressor of fused (SuFu) on glioma-associated oncogene homologue 1 (Gli1) regulate its nuclear localization

Gajewska, K, Kaur, G, Wagstaff, KM, Wang, C, Loveland, KL, Ly-Huynh, J, Davies, RG, Szczepny, A, Jans, DA, Dias, M

Biochem. J. 2014
16061793 Cilia and Hedgehog responsiveness in the mouse

Huangfu, D, Anderson, KV

Proc. Natl. Acad. Sci. U.S.A. 2005
19371734 Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia

Zeng, H, Liu, A, Kolterud, A, Toftgård, R, Hoover, A, Jia, J, Teglund, S

Dev. Biol. 2009
11960000 Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex

Bishop, JM, Cheng, SY

Proc. Natl. Acad. Sci. U.S.A. 2002
12426310 Characterization of the physical interaction of Gli proteins with SUFU proteins

Kogerman, P, Toftgard, R, Dunaeva, M, Michelson, P

J. Biol. Chem. 2003
12068298 Mutations in SUFU predispose to medulloblastoma

Hao, A, Zhang, X, Stavrou, T, Lowrance, A, Dura, WT, Goldstein, AM, Agatep, R, Chiappa, S, Mainprize, TG, Taylor, MD, Gao, L, Raffel, C, Rutka, JT, Wainwright, B, Scherer, SW, Hui, CC, Hogg, D, Squire, JA, Liu, L

Nat. Genet. 2002
10564661 Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli

Rosenthal, A, Armanini, MP, Goddard, A, Murone, M, Ye, W, de Sauvage, FJ, Gurney, A, Stone, DM, Phillips, H, Brush, J, Luoh, S

J. Cell. Sci. 1999
16459298 Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway

Heby-Henricson, K, Henricson, KH, Toftgård, R, Bergström, A, Lauth, M, Rozell, B, Ericson, J, Svärd, J, Persson-Lek, M, Teglund, S

Dev. Cell 2006
10433824 Vertebrate homologs of Drosophila suppressor of fused interact with the gli family of transcriptional regulators

Tabin, CJ, Collier, LS, Scott, MP, Pearse, RV

Dev. Biol. 1999
19533801 Identification of a SUFU germline mutation in a family with Gorlin syndrome

Marzocchi, C, Pastorino, L, Nasti, S, Cusano, R, Scarrà, GB, Clementi, M, Garrè, ML, Battistuzzi, L, Ghiorzo, P

Am. J. Med. Genet. A 2009
19684112 Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved

Li, YJ, Zhang, X, Hui, CC, Chuang, PT, Gacayan, R, Law, KK, Wilson, CW, Lu, CS, Chen, MH

Genes Dev. 2009
16155214 Cardiac and CNS defects in a mouse with targeted disruption of suppressor of fused

Johnson, L, Yu, KP, Brueckner, M, Brailey, LL, Cooper, AF, Bale, AE, McGrath, JM

Development 2005
9601642 Suppressor of fused links fused and Cubitus interruptus on the hedgehog signalling pathway

Plessis, A, Dussillol, F, Monnier, V, Alves, G, Lamour-Isnard, C

Curr Biol 1998
14611647 The negative regulator of Gli, Suppressor of fused (Sufu), interacts with SAP18, Galectin3 and other nuclear proteins

Paces-Fessy, M, Petit, E, Paute-Briand, S, Boucher, D, Blanchet-Tournier, MF

Biochem. J. 2004
20360384 The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins

Milenkovic, L, Rohatgi, R, Scott, MP, Humke, EW, Dorn, KV

Genes Dev. 2010
20956384 A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes

Salic, A, Lopez, LV, Tukachinsky, H

J. Cell Biol. 2010
19622347 Sufu recruits GSK3beta for efficient processing of Gli3

Morinaka, A, Miki, H, Kise, Y, Teglund, S

Biochem. Biophys. Res. Commun. 2009
Participants
Participates
Orthologous Events
Authored
Reviewed
Created
Cite Us!