Reactome | GLI:SUFU dissociates

GLI:SUFU dissociates

Stable Identifier

R-HSA-5635859

Type

Reaction [dissociation]

Species

Homo sapiens

Compartment

ciliary tip

ReviewStatus

5/5

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Hh signaling promotes the dissociation of the GLI:SUFU complex in the cilium downstream of SMO activation (Humke et al, 2010; Tukachinsky et al, 2010). This appears to divert the transcription factors away from the partial processing/degradation pathway and allow the full-length forms to translocate to the nucleus where they are converted to labile transcriptional activators (Humke et al, 2010; Tukachinsky et al, 2010; Pan et al, 2006; Kim et al, 2009). How the Hh signal is transmited from SMO to promote the dissociation of the GLI:SUFU complex is not clear, however it may involve changes in PKA activity as a result of lowered cAMP levels upon pathway stimulation. (Tukachinsky et al, 2010; Wen et al, 2010; Tuson et al, 2011; Barzi et al, 2010; reviewed in Briscoe and Therond, 2013). GPR161, which localizes to the cilium in a TULP3-dependent manner and which increases cAMP levels in the absence of ligand, is cleared from the cilium upon pathway activation, and deletion of GPR161 increases Hh-dependent signaling (Mukhopadhyay et al, 2010; Mukhopadhyay et al, 2013). These data suggest that removal of ciliary GPR161 upon Hh stimulation may contribute to pathway activity by downregulating PKA activity through cAMP levels (reviewed in Mukhopadhyay and Rohatgi, 2014).

Literature References

PubMed ID	Title	Journal	Year
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 Scales, SJ, Hongo, JA, Wen, X, Evangelista, M, Lai, CK, de Sauvage, FJ	Mol. Cell. Biol.	2010
22007132	Protein kinase A acts at the basal body of the primary cilium to prevent Gli2 activation and ventralization of the mouse neural tube Tuson, M, He, M, Anderson, KV	Development	2011
23332756	The ciliary G-protein-coupled receptor Gpr161 negatively regulates the Sonic hedgehog pathway via cAMP signaling Scales, SJ, Wen, X, Rangell, L, Jackson, PK, Loktev, A, Mukhopadhyay, S, Ratti, N	Cell	2013
16611981	Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation Pan, Y, Bai, CB, Wang, B, Joyner, AL	Mol. Cell. Biol.	2006
20889716	TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia Lane, WS, Scales, SJ, Wen, X, Chih, B, Jackson, PK, Nelson, CD, Mukhopadhyay, S	Genes Dev.	2010
23719536	The mechanisms of Hedgehog signalling and its roles in development and disease Thérond, PP, Briscoe, J	Nat. Rev. Mol. Cell Biol.	2013
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
24845016	G-protein-coupled receptors, Hedgehog signaling and primary cilia Rohatgi, R, Mukhopadhyay, S	Semin. Cell Dev. Biol.	2014
20016067	Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base Barzi, M, Pons, S, Alvarez-Rodriguez, R, Berenguer, J, Menendez, A	J. Cell. Sci.	2010