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Article

Kinetics of Hedgehog-Dependent Full-Length Gli3 Accumulation in Primary Cilia and Subsequent Degradation

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Pages 1910-1922 | Received 14 Aug 2009, Accepted 29 Jan 2010, Published online: 20 Mar 2023

REFERENCES

  • Agren, M., P. Kogerman, M. I. Kleman, M. Wessling, and R. Toftgard. 2004. Expression of the PTCH1 tumor suppressor gene is regulated by alternative promoters and a single functional Gli-binding site. Gene 330:101–114.
  • Alexandre, C., A. Jacinto, and P. W. Ingham. 1996. Transcriptional activation of Hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. Genes Dev. 10:2003–2013.
  • Aza-Blanc, P., H. Y. Lin, A. Ruiz i Altaba, and T. B. Kornberg. 2000. Expression of the vertebrate Gli proteins in Drosophila reveals a distribution of activator and repressor activities. Development 127:4293–4301.
  • Aza-Blanc, P., F. A. Ramirez-Weber, M. P. Laget, C. Schwartz, and T. B. Kornberg. 1997. Proteolysis that is inhibited by Hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor. Cell 89:1043–1053.
  • Brooks, P., G. Fuertes, R. Z. Murray, S. Bose, E. Knecht, M. C. Rechsteiner, K. B. Hendil, K. Tanaka, J. Dyson, and J. Rivett. 2000. Subcellular localization of proteasomes and their regulatory complexes in mammalian cells. Biochem. J. 346:155–161.
  • Caspary, T., C. E. Larkins, and K. V. Anderson. 2007. The graded response to Sonic Hedgehog depends on cilia architecture. Dev. Cell 12:767–778.
  • Chang, D. T., A. Lopez, D. P. von Kessler, C. Chiang, B. K. Simandl, R. Zhao, M. F. Seldin, J. F. Fallon, and P. A. Beachy. 1994. Products, genetic linkage and limb patterning activity of a murine Hedgehog gene. Development 120:3339–3353.
  • Chen, C. H., D. P. von Kessler, W. Park, B. Wang, Y. Ma, and P. A. Beachy. 1999. Nuclear trafficking of Cubitus interruptus in the transcriptional regulation of Hedgehog target gene expression. Cell 98:305–316.
  • Chen, J. K., J. Taipale, M. K. Cooper, and P. A. Beachy. 2002. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 16:2743–2748.
  • Chen, M. H., C. W. Wilson, Y. J. Li, K. K. Law, C. S. Lu, R. Gacayan, X. Zhang, C. C. Hui, and P. T. Chuang. 2009. Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes Dev. 23:1910–1928.
  • Chen, Y., V. Knezevic, V. Ervin, R. Hutson, Y. Ward, and S. Mackem. 2004. Direct interaction with Hoxd proteins reverses Gli3-repressor function to promote digit formation downstream of Shh. Development 131:2339–2347.
  • Cho, A., H. W. Ko, and J. T. Eggenschwiler. 2008. FKBP8 cell-autonomously controls neural tube patterning through a Gli2- and Kif3a-dependent mechanism. Dev. Biol. 321:27–39.
  • Corbit, K. C., P. Aanstad, V. Singla, A. R. Norman, D. Y. Stainier, and J. F. Reiter. 2005. Vertebrate Smoothened functions at the primary cilium. Nature 437:1018–1021.
  • Cortellino, S., C. Wang, B. Wang, M. R. Bassi, E. Caretti, D. Champeval, A. Calmont, M. Jarnik, J. Burch, K. S. Zaret, L. Larue, and A. Bellacosa. 2009. Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4. Dev. Biol. 325:225–237.
  • Dai, P., H. Akimaru, Y. Tanaka, T. Maekawa, M. Nakafuku, and S. Ishii. 1999. Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3. J. Biol. Chem. 274:8143–8152.
  • Eggenschwiler, J. T., and K. V. Anderson. 2007. Cilia and developmental signaling. Annu. Rev. Cell Dev. Biol. 23:345–373.
  • Eggenschwiler, J. T., O. V. Bulgakov, J. Qin, T. Li, and K. V. Anderson. 2006. Mouse Rab23 regulates Hedgehog signaling from smoothened to Gli proteins. Dev. Biol. 290:1–12.
  • Endoh-Yamagami, S., M. Evangelista, D. Wilson, X. Wen, J.-W. Theunissen, K. Phamluong, M. Davis, S. J. Scales, M. J. Solloway, F. J. de Sauvage, and A. S. Peterson. 2009. The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development. Curr. Biol. 19:1320–1326.
  • Evan, G. I., G. K. Lewis, G. Ramsay, and J. M. Bishop. 1985. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol. Cell. Biol. 5:3610–3616.
  • Evangelista, M., T. Y. Lim, J. Lee, L. Parker, A. Ashique, A. S. Peterson, W. Ye, D. P. Davis, and F. J. de Sauvage. 2008. Kinome siRNA screen identifies regulators of ciliogenesis and hedgehog signal transduction. Sci. Signal 1:ra7.
  • Frank-Kamenetsky, M., X. M. Zhang, S. Bottega, O. Guicherit, H. Wichterle, H. Dudek, D. Bumcrot, F. Y. Wang, S. Jones, J. Shulok, L. L. Rubin, and J. A. Porter. 2002. Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists. J. Biol. 1 (2):10.
  • Freed, E., K. R. Lacey, P. Huie, S. A. Lyapina, R. J. Deshaies, T. Stearns, and P. K. Jackson. 1999. Components of an SCF ubiquitin ligase localize to the centrosome and regulate the centrosome duplication cycle. Genes Dev. 13:2242–2257.
  • Fumoto, K., C. C. Hoogenraad, and A. Kikuchi. 2006. GSK-3β-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome. EMBO J. 25:5670–5682.
  • Hammerschmidt, M., M. J. Bitgood, and A. P. McMahon. 1996. Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo. Genes Dev. 10:647–658.
  • Haycraft, C. J., B. Banizs, Y. Aydin-Son, Q. Zhang, E. J. Michaud, and B. K. Yoder. 2005. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet 1:e53.
  • Hill, P., K. Gotz, and U. Ruther. 2009. A SHH-independent regulation of Gli3 is a significant determinant of anteroposterior patterning of the limb bud. Dev. Biol. 328:506–516.
  • Hongo, J. A., M. Mora-Worms, C. Lucas, and B. M. Fendly. 1995. Development and characterization of murine monoclonal antibodies to the latency-associated peptide of transforming growth factor beta 1. Hybridoma 14:253–260.
  • Huangfu, D., and K. V. Anderson. 2005. Cilia and Hedgehog responsiveness in the mouse. Proc. Natl. Acad. Sci. U. S. A. 102:11325–11330.
  • Huangfu, D., A. Liu, A. S. Rakeman, N. S. Murcia, L. Niswander, and K. V. Anderson. 2003. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426:83–87.
  • Ingham, P. W., and A. P. McMahon. 2001. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 15:3059–3087.
  • Jia, H., Y. Liu, W. Yan, and J. Jia. 2009. PP4 and PP2A regulate Hedgehog signaling by controlling Smo and Ci phosphorylation. Development 136:307–316.
  • Jiang, J. 2006. Regulation of Hh/Gli signaling by dual ubiquitin pathways. Cell Cycle 5:2457–2463.
  • Jiang, J., and C. C. Hui. 2008. Hedgehog signaling in development and cancer. Dev. Cell 15:801–812.
  • Kalderon, D. 2000. Transducing the Hedgehog signal. Cell 103:371–374.
  • Kent, D., E. W. Bush, and J. E. Hooper. 2006. Roadkill attenuates Hedgehog responses through degradation of Cubitus interruptus. Development 133:2001–2010.
  • Kiprilov, E. N., A. Awan, R. Desprat, M. Velho, C. A. Clement, A. G. Byskov, C. Y. Andersen, P. Satir, E. E. Bouhassira, S. T. Christensen, and R. E. Hirsch. 2008. Human embryonic stem cells in culture possess primary cilia with Hedgehog signaling machinery. J. Cell Biol. 180:897–904.
  • Kirchhofer, D., M. Peek, W. Li, J. Stamos, C. Eigenbrot, S. Kadkhodayan, J. M. Elliott, R. T. Corpuz, R. A. Lazarus, and P. Moran. 2003. Tissue expression, protease specificity, and Kunitz domain functions of hepatocyte growth factor activator inhibitor-1B (HAI-1B), a new splice variant of HAI-1. J. Biol. Chem. 278:36341–36349.
  • Kohler, G., and C. Milstein. 1975. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497.
  • Kozminski, K. G., K. A. Johnson, P. Forscher, and J. L. Rosenbaum. 1993. A motility in the eukaryotic flagellum unrelated to flagellar beating. Proc. Natl. Acad. Sci. U. S. A. 90:5519–5523.
  • Kwon, J. E., M. La, K. H. Oh, Y. M. Oh, G. R. Kim, J. H. Seol, S. H. Baek, T. Chiba, K. Tanaka, O. S. Bang, C. O. Joe, and C. H. Chung. 2006. BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase. J. Biol. Chem. 281:12664–12672.
  • Litingtung, Y., and C. Chiang. 2000. Specification of ventral neuron types is mediated by an antagonistic interaction between Shh and Gli3. Nat. Neurosci. 3:979–985.
  • Litingtung, Y., R. D. Dahn, Y. Li, J. F. Fallon, and C. Chiang. 2002. Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity. Nature 418:979–983.
  • Liu, A., B. Wang, and L. A. Niswander. 2005. Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors. Development 132:3103–3111.
  • Lum, L., and P. A. Beachy. 2004. The Hedgehog response network: sensors, switches, and routers. Science 304:1755–1759.
  • Marigo, V., R. L. Johnson, A. Vortkamp, and C. J. Tabin. 1996. Sonic Hedgehog differentially regulates expression of GLI and GLI3 during limb development. Dev. Biol. 180:273–283.
  • Masyuk, A. I., S. A. Gradilone, J. M. Banales, B. Q. Huang, T. V. Masyuk, S. O. Lee, P. L. Splinter, A. J. Stroope, and N. F. Larusso. 2008. Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors. Am. J. Physiol. Gastrointest. Liver Physiol. 295:G725–G734.
  • May, S. R., A. M. Ashique, M. Karlen, B. Wang, Y. Shen, K. Zarbalis, J. Reiter, J. Ericson, and A. S. Peterson. 2005. Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli. Dev. Biol. 287:378–389.
  • McEvoy, J. D., U. Kossatz, N. Malek, and J. D. Singer. 2007. Constitutive turnover of cyclin E by Cul3 maintains quiescence. Mol. Cell. Biol. 27:3651–3666.
  • McMahon, A. P., P. W. Ingham, and C. J. Tabin. 2003. Developmental roles and clinical significance of Hedgehog signaling. Curr. Top. Dev. Biol. 53:1–114.
  • Nagai, Y., T. Kojima, Y. Muro, T. Hachiya, Y. Nishizawa, T. Wakabayashi, and M. Hagiwara. 1997. Identification of a novel nuclear speckle-type protein, SPOP. FEBS Lett. 418:23–26.
  • Nielsen, S. K., K. Mollgard, C. A. Clement, I. R. Veland, A. Awan, B. K. Yoder, I. Novak, and S. T. Christensen. 2008. Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines. Dev. Dyn. 237:2039–2052.
  • Norman, R. X., H. W. Ko, V. Huang, C. M. Eun, L. L. Abler, Z. Zhang, X. Sun, and J. T. Eggenschwiler. 2009. Tubby-like protein 3 (TULP3) regulates patterning in the mouse embryo through inhibition of Hedgehog signaling. Hum. Mol. Genet. 18:1740–1754.
  • Nybakken, K., and N. Perrimon. 2002. Hedgehog signal transduction: recent findings. Curr. Opin. Genet. Dev. 12:503–511.
  • Ocbina, P. J., and K. V. Anderson. 2008. Intraflagellar transport, cilia, and mammalian Hedgehog signaling: analysis in mouse embryonic fibroblasts. Dev. Dyn. 237:2030–2038.
  • Ou, C. Y., Y. F. Lin, Y. J. Chen, and C. T. Chien. 2002. Distinct protein degradation mechanisms mediated by Cul1 and Cul3 controlling Ci stability in Drosophila eye development. Genes Dev. 16:2403–2414.
  • Pan, Y., C. B. Bai, A. L. Joyner, and B. Wang. 2006. Sonic Hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation. Mol. Cell. Biol. 26:3365–3377.
  • Pan, Y., and B. Wang. 2007. A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome. J. Biol. Chem. 282:10846–10852.
  • Pan, Y., C. Wang, and B. Wang. 2009. Phosphorylation of Gli2 by protein kinase A is required for Gli2 processing and degradation and the Sonic Hedgehog-regulated mouse development. Dev. Biol. 326:177–189.
  • Patterson, V. L., C. Damrau, A. Paudyal, B. Reeve, D. T. Grimes, M. E. Stewart, D. J. Williams, P. Siggers, A. Greenfield, and J. N. Murdoch. 2009. 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. 18:1719–1739.
  • Porter, M. E., and W. S. Sale. 2000. The 9 + 2 axoneme anchors multiple inner arm dyneins and a network of kinases and phosphatases that control motility. J. Cell Biol. 151:F37–F42.
  • Reiter, J. F., and W. C. Skarnes. 2006. Tectonic, a novel regulator of the Hedgehog pathway required for both activation and inhibition. Genes Dev. 20:22–27.
  • Riobo, N. A., and D. R. Manning. 2007. Pathways of signal transduction employed by vertebrate Hedgehogs. Biochem. J. 403:369–379.
  • Rogers, G. C., N. M. Rusan, D. M. Roberts, M. Peifer, and S. L. Rogers. 2009. The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. J. Cell Biol. 184:225–239.
  • Rohatgi, R., L. Milenkovic, R. B. Corcoran, and M. P. Scott. 2009. Hedgehog signal transduction by Smoothened: pharmacologic evidence for a 2-step activation process. Proc. Natl. Acad. Sci. U. S. A. 106:3196–3201.
  • Rohatgi, R., L. Milenkovic, and M. P. Scott. 2007. Patched 1 regulates Hedgehog signaling at the primary cilium. Science 317:372–376.
  • Rohatgi, R., and M. P. Scott. 2007. Patching the gaps in Hedgehog signalling. Nat. Cell Biol. 9:1005–1009.
  • Romer, J. T., H. Kimura, S. Magdaleno, K. Sasai, C. Fuller, H. Baines, M. Connelly, C. F. Stewart, S. Gould, L. L. Rubin, and T. Curran. 2004. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1+/− p53−/− mice. Cancer Cell 6:229–240.
  • Ruiz i Altaba, A., C. Mas, and B. Stecca. 2007. The Gli code: an information nexus regulating cell fate, stemness and cancer. Trends Cell Biol. 17:438–447.
  • Ruppert, J. M., K. W. Kinzler, A. J. Wong, S. H. Bigner, F. T. Kao, M. L. Law, H. N. Seuanez, S. J. O'Brien, and B. Vogelstein. 1988. The GLI-Kruppel family of human genes. Mol. Cell. Biol. 8:3104–3113.
  • Ruppert, J. M., B. Vogelstein, K. Arheden, and K. W. Kinzler. 1990. GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity. Mol. Cell. Biol. 10:5408–5415.
  • Salathe, M. 2007. Regulation of mammalian ciliary beating. Annu. Rev. Physiol. 69:401–422.
  • Sasaki, H., Y. Nishizaki, C. Hui, M. Nakafuku, and H. Kondoh. 1999. Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling. Development 126:3915–3924.
  • Scales, S. J., and F. J. de Sauvage. 2009. Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol. Sci. 30:303–312.
  • Schweitzer, R., K. J. Vogan, and C. J. Tabin. 2000. Similar expression and regulation of Gli2 and Gli3 in the chick limb bud. Mech. Dev. 98:171–174.
  • Sheng, T., S. Chi, X. Zhang, and J. Xie. 2006. Regulation of Gli1 localization by the cAMP/protein kinase A signaling axis through a site near the nuclear localization signal. J. Biol. Chem. 281:9–12.
  • Shin, S. H., P. Kogerman, E. Lindstrom, R. Toftgard, and L. G. Biesecker. 1999. GLI3 mutations in human disorders mimic Drosophila cubitus interruptus protein functions and localization. Proc. Natl. Acad. Sci. U. S. A. 96:2880–2884.
  • Sillibourne, J. E., D. M. Milne, M. Takahashi, Y. Ono, and D. W. Meek. 2002. Centrosomal anchoring of the protein kinase CK1δ mediated by attachment to the large, coiled-coil scaffolding protein CG-NAP/AKAP450. J. Mol. Biol. 322:785–797.
  • Stone, D. M., M. Murone, S. Luoh, W. Ye, M. P. Armanini, A. Gurney, H. Phillips, J. Brush, A. Goddard, F. J. de Sauvage, and A. Rosenthal. 1999. Characterization of the human suppressor of Fused, a negative regulator of the zinc-finger transcription factor Gli. J. Cell Sci. 112:4437–4448.
  • Taipale, J., M. K. Cooper, T. Maiti, and P. A. Beachy. 2002. Patched acts catalytically to suppress the activity of Smoothened. Nature 418:892–897.
  • Taylor, F. R., D. Wen, E. A. Garber, A. N. Carmillo, D. P. Baker, R. M. Arduini, K. P. Williams, P. H. Weinreb, P. Rayhorn, X. Hronowski, A. Whitty, E. S. Day, A. Boriack-Sjodin, R. I. Shapiro, A. Galdes, and R. B. Pepinsky. 2001. Enhanced potency of human Sonic Hedgehog by hydrophobic modification. Biochemistry 40:4359–4371.
  • Tempe, D., M. Casas, S. Karaz, M. F. Blanchet-Tournier, and J. P. Concordet. 2006. Multisite protein kinase A and glycogen synthase kinase 3β phosphorylation leads to Gli3 ubiquitination by SCFβTrCP. Mol. Cell. Biol. 26:4316–4326.
  • te Welscher, P., A. Zuniga, S. Kuijper, T. Drenth, H. J. Goedemans, F. Meijlink, and R. Zeller. 2002. Progression of vertebrate limb development through SHH-mediated counteraction of GLI3. Science 298:827–830.
  • Tian, L., R. A. Holmgren, and A. Matouschek. 2005. A conserved processing mechanism regulates the activity of transcription factors Cubitus interruptus and NF-κB. Nat. Struct. Mol. Biol. 12:1045–1053.
  • Tran, P. V., C. J. Haycraft, T. Y. Besschetnova, A. Turbe-Doan, R. W. Stottmann, B. J. Herron, A. L. Chesebro, H. Qiu, P. J. Scherz, J. V. Shah, B. K. Yoder, and D. R. Beier. 2008. THM1 negatively modulates mouse sonic Hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat. Genet 40:403–410.
  • Varjosalo, M., M. Bjorklund, F. Cheng, H. Syvanen, T. Kivioja, S. Kilpinen, Z. Sun, O. Kallioniemi, H. G. Stunnenberg, W. W. He, P. Ojala, and J. Taipale. 2008. Application of active and kinase-deficient kinome collection for identification of kinases regulating Hedgehog signaling. Cell 133:537–548.
  • Varjosalo, M., and J. Taipale. 2008. Hedgehog: functions and mechanisms. Genes Dev. 22:2454–2472.
  • Wang, B., J. F. Fallon, and P. A. Beachy. 2000. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell 100:423–434.
  • Wang, B., and Y. Li. 2006. Evidence for the direct involvement of βTrCP in Gli3 protein processing. Proc. Natl. Acad. Sci. U. S. A. 103:33–38.
  • Wang, C., U. Ruther, and B. Wang. 2007. The Shh-independent activator function of the full-length Gli3 protein and its role in vertebrate limb digit patterning. Dev. Biol. 305:460–469.
  • Wang, G., B. Wang, and J. Jiang. 1999. Protein kinase A antagonizes Hedgehog signaling by regulating both the activator and repressor forms of Cubitus interruptus. Genes Dev. 13:2828–2837.
  • Wang, Y., Z. Zhou, C. T. Walsh, and A. P. McMahon. 2009. Selective translocation of intracellular Smoothened to the primary cilium in response to Hedgehog pathway modulation. Proc. Natl. Acad. Sci. U. S. A. 106:2623–2628.
  • Wigley, W. C., R. P. Fabunmi, M. G. Lee, C. R. Marino, S. Muallem, G. N. DeMartino, and P. J. Thomas. 1999. Dynamic association of proteasomal machinery with the centrosome. J. Cell Biol. 145:481–490.
  • Wilson, C. W., M. H. Chen, and P. T. Chuang. 2009. Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium. PLoS One 4:e5182.
  • Wong, S. Y., and J. F. Reiter. 2008. The primary cilium at the crossroads of mammalian Hedgehog signaling. Curr. Top. Dev. Biol. 85:225–260.
  • Wu, J. T., H. C. Lin, Y. C. Hu, and C. T. Chien. 2005. Neddylation and deneddylation regulate Cul1 and Cul3 protein accumulation. Nat. Cell Biol. 7:1014–1020.
  • Yauch, R. L., S. E. Gould, S. J. Scales, T. Tang, H. Tian, C. P. Ahn, D. Marshall, L. Fu, T. Januario, D. Kallop, M. Nannini-Pepe, K. Kotkow, J. C. Marsters, L. L. Rubin, and F. J. de Sauvage. 2008. A paracrine requirement for Hedgehog signalling in cancer. Nature 455:406–410.
  • Zhang, Q., L. Zhang, B. Wang, C. Y. Ou, C. T. Chien, and J. Jiang. 2006. A Hedgehog-induced BTB protein modulates Hedgehog signaling by degrading Ci/Gli transcription factor. Dev. Cell 10:719–729.

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