Reference Report

Reference
Citation	Mosimann, C., Hausmann, G., Basler, K. (2009). The role of Parafibromin/Hyrax as a nuclear Gli/Ci-interacting protein in Hedgehog target gene control. Mech. Dev. 126(5-6): 394--405. (Export to RIS)
FlyBase ID	FBrf0207957
Publication Type	Research paper
PubMed ID	19368795
PubMed Abstract	The Hedgehog (Hh) pathway, an evolutionarily conserved key regulator of embryonic patterning and tissue homeostasis, controls its target genes by managing the processing and activities of the Gli/Ci transcription factors. Little is known about the nuclear co-factors the Gli/Ci proteins recruit, and how they mechanistically control Hh target genes. Here, we provide evidence for the involvement of Parafibromin/Hyx as a positive component in Hh signaling. We found that hyx RNAi impaired Hh pathway activity in Drosophila cell culture. Consistent with an evolutionarily conserved function in Hh signaling, RNAi-mediated knockdown of Parafibromin in mammalian cell culture experiments diminished the transcriptional activity of Gli1 and Gli2. In vivo, in Drosophila, genetic impairment of hyx decreased the expression of the high-threshold Hh target gene knot/collier. Conversely, hyx overexpression ameliorated the inhibitory activity of Ptc and Ci(75) misexpression during Drosophila wing development. We subsequently found that Parafibromin can form a complex with all three Glis, and provide evidence that Parafibromin/Hyx directly binds Region 1, the Su(fu) interaction domain, in the N-terminus of all Glis and Ci. Taken together, our results suggest a target gene-selective involvement of the PAF1 complex in Hh signaling via the Parafibromin/Hyx-mediated recruitment to Gli/Ci.
DOI	10.1016/j.mod.2009.02.002
Related Publication(s)
Personal communication to FlyBase	spalt major-Gal4 lines. de Celis and Basler, 2010.7.11, spalt major-Gal4 lines. [FBrf0211371]
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Secondary IDs
Language of Publication	English
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Parent Publication
Publication Type	Journal
Abbreviation	Mech. Dev.
Title	Mechanisms of Development
Publication Year	1990-
ISBN/ISSN	0925-4773
Data from Reference
Alleles (13)
	Avic\GFP^{Scer\UAS.T:SV40\nls2} ci^75.Scer\UAS ci^{PKA1.Scer\UAS.T:Ivir\HA1} Hsap\CDC73^Scer\UAS.cMa hyx¹ hyx² hyx^EP9 hyx^EY06898 hyx^Scer\UAS.cMa ptc^{Scer\UAS.T:Hsap\MYC} Scer\GAL4^C-765 Scer\GAL4^nub-AC-62 Scer\GAL4^salm.E
Constructs (7)
	P{salm-GAL4.E} P{UAS-ci.75} P{UAS-ci.PKA1} P{UAS-GFP.nls} P{UAS-HRPT2.M} P{UAS-hyx.M} P{UAS-ptc.wt-myc}
Genes (11)
	Avic\GFP ci cos dpp en Hsap\CDC73 hyx kn ptc Scer\GAL4 smo
Insertions (3)
	P{EP}hyx^EP9 P{GawB}C-765 P{GawB}nubbin-AC-62
Natural transposons (1)
	P-element