Reactome | GLI:SUFU translocates to the ciliary tip in response to Hh signaling

GLI:SUFU translocates to the ciliary tip in response to Hh signaling

Stable Identifier

R-HSA-5635860

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

ciliary tip

ReviewStatus

5/5

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GLI:SUFU translocates to the ciliary tip in response to Hh signaling

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Activation of the Hh pathway causes the GLI:SUFU complex to concentrate in the primary cilium (Humke et al, 2010; Tukachinsky et al, 2010; Kim et al, 2009). The net movement of the GLI:SUFU complex into the cilium occurs downstream of SMO phosphorylation and activation, and requires the Cos2 homologue KIF7, but how the signal is transmitted from the SMO:EVC complex is not clear (Chen et al, 2009; Chen et al, 2010; Pusapati et al, 2013; Endoh-Yamagami et al, 2009; Liem et al, 2009; Cheung et al, 2009). SUFU appears to be a major regulator of the ratio of full length:repressor forms of GLI proteins in vertebrate cells, and the GLI:SUFU interaction is required for the production of GLIR. Dissociation of the GLI:SUFU complex after ligand stimulation diverts GLI from the degradation pathway and allows the full-length form to be activated (Humke et al, 2010; Tukachinsky et al, 2010; Pan et al, 2006; Kim et al, 209; Wen et al, 2010; Chen et al, 2009; reviewed in Briscoe and Therond, 2013). This represents another major point of divergence between the fly and the vertebrate Hh pathways. In Drosophila, absence of SUFU has no effect on Hh signaling, and the scaffolding protein Cos2 may play the key inhibitory role (Varjosalo et al, 2006; reviewed in Briscoe and Therond, 2013).

Literature References

PubMed ID	Title	Journal	Year
21695114	Sonic Hedgehog dependent phosphorylation by CK1? and GRK2 is required for ciliary accumulation and activation of smoothened Chen, Y, Sasai, N, Ma, G, Yue, T, Jia, J, Briscoe, J, Jiang, J	PLoS Biol.	2011
19592253	The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development Endoh-Yamagami, S, Evangelista, M, Wilson, D, Wen, X, Theunissen, JW, Phamluong, K, Davis, M, Scales, SJ, Solloway, MJ, de Sauvage, FJ, Peterson, AS	Curr. Biol.	2009
19996169	Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus Kim, J, Kato, M, Beachy, PA	Proc. Natl. Acad. Sci. U.S.A.	2009
20154143	Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation Wen, X, Lai, CK, Evangelista, M, Hongo, JA, de Sauvage, FJ, Scales, SJ	Mol. Cell. Biol.	2010
16459297	Divergence of hedgehog signal transduction mechanism between Drosophila and mammals Varjosalo, M, Li, SP, Taipale, J	Dev. Cell	2006
23719536	The mechanisms of Hedgehog signalling and its roles in development and disease Briscoe, J, Thérond, PP	Nat. Rev. Mol. Cell Biol.	2013
19666503	Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling Liem, KF, He, M, Ocbina, PJ, Anderson, KV	Proc. Natl. Acad. Sci. U.S.A.	2009
20844016	G protein-coupled receptor kinase 2 promotes high-level Hedgehog signaling by regulating the active state of Smo through kinase-dependent and kinase-independent mechanisms in Drosophila Chen, Y, Li, S, Tong, C, Zhao, Y, Wang, B, Liu, Y, Jia, J, Jiang, J	Genes Dev.	2010
19549984	The kinesin protein Kif7 is a critical regulator of Gli transcription factors in mammalian hedgehog signaling Cheung, HO, Zhang, X, Ribeiro, A, Mo, R, Makino, S, Puviindran, V, Law, KK, Briscoe, J, Hui, CC	Sci Signal	2009
19684112	Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved Chen, MH, Wilson, CW, Li, YJ, Law, KK, Lu, CS, Gacayan, R, Zhang, X, Hui, CC, Chuang, PT	Genes Dev.	2009
16611981	Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation Pan, Y, Bai, CB, Joyner, AL, Wang, B	Mol. Cell. Biol.	2006
20360384	The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins Humke, EW, Dorn, KV, Milenkovic, L, Scott, MP, Rohatgi, R	Genes Dev.	2010
20956384	A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes Tukachinsky, H, Lopez, LV, Salic, A	J. Cell Biol.	2010
24582806	EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to the base of primary cilia Pusapati, GV, Hughes, CE, Dorn, KV, Zhang, D, Sugianto, P, Aravind, L, Rohatgi, R	Dev. Cell	2014