Reference Report

Reference
Citation	Du, J., Zhang, J., Su, Y., Liu, M., Ospina, J.K., Yang, S., Zhu, A.J. (2011). In Vivo RNAi Screen Reveals Neddylation Genes as Novel Regulators of Hedgehog Signaling. PLoS ONE 6(9): e24168. (Export to RIS)
FlyBase ID	FBrf0215574
Publication Type	Research paper
PubMed ID	21931660
PubMed Abstract	Hedgehog (Hh) signaling is highly conserved in all metazoan animals and plays critical roles in many developmental processes. Dysregulation of the Hh signaling cascade has been implicated in many diseases, including cancer. Although key components of the Hh pathway have been identified, significant gaps remain in our understanding of the regulation of individual Hh signaling molecules. Here, we report the identification of novel regulators of the Hh pathway, obtained from an in vivo RNA interference (RNAi) screen in Drosophila. By selectively targeting critical genes functioning in post-translational modification systems utilizing ubiquitin (Ub) and Ub-like proteins, we identify two novel genes (dUba3 and dUbc12) that negatively regulate Hh signaling activity. We provide in vivo and in vitro evidence illustrating that dUba3 and dUbc12 are essential components of the neddylation pathway; they function in an enzyme cascade to conjugate the ubiquitin-like NEDD8 modifier to Cullin proteins. Neddylation activates the Cullin-containing ubiquitin ligase complex, which in turn promotes the degradation of Cubitus interruptus (Ci), the downstream transcription factor of the Hh pathway. Our study reveals a conserved molecular mechanism of the neddylation pathway in Drosophila and sheds light on the complex post-translational regulations in Hh signaling.
DOI	10.1371/journal.pone.0024168
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Language of Publication	English
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Publication Type	Journal
Abbreviation	PLoS ONE
Title	PLoS ONE
Publication Year	2006-
ISBN/ISSN	1932-6203
Data from Reference
Alleles (26)
	car^HMS00972 dor⁸ dor^GD10124 dor^KK102176 Ecol\lacZ^dpp.BS3.0 Hrs^D28 Hrs^JF02860 Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} Nedd8^AN015 Prosβ2^1.Scer\UAS Prosβ6^1.B.Scer\UAS Rpn6^GD6881 Rpn8^GD10960 Scer\GAL4^Act5C.PI Scer\GAL4^ap-md544 Scer\GAL4^Bx-MS1096 Scer\GAL4^{Scer\FRT.Act5C} Scer\UBP2^Scer\UAS.cDa Stam^2L3297 Stam^GD11948 Uba3^GD7988 Uba3^KK102057 Uba3^SH2028 Ubc12^GD12219 Ubc12^KK108493 Ubc12^LL04684
Constructs (18)
	P{Act5C-GAL4} P{AyGAL4} P{BS3.0} P{GD6881} P{GD7988} P{GD10124} P{GD10960} P{GD11948} P{GD12219} P{KK102057} P{KK102176} P{KK108493} P{TRiP.HMS00972} P{TRiP.JF02860} P{UAS-mCD8::GFP.L} P{UAS-Pros26¹.B} P{UAS-Prosβ2¹} P{UAS-UBP2.D}
Genes (23)
	APP-BP1 car ci Cul-3 Dl dor Ecol\lacZ Hrs kn lin19 Mmus\Cd8a Nedd8 Prosβ2 Prosβ6 Roc1a Rpn6 Rpn8 Scer\GAL4 Scer\UBP2 slmb Stam Uba3 Ubc12
Insertions (15)
	P{GawB}ap^md544 P{GawB}Bx^MS1096 P{GD6881}v18021 P{GD7988}v17137 P{GD7988}v17139 P{GD10124}v33733 P{GD10960}v26183 P{GD11948}v22497 P{GD12219}v35219 P{GD12219}v35220 P{KK102057}VIE-260B P{KK102176}VIE-260B P{KK108493}VIE-260B P{TRiP.JF02860}attP2 PBac{SAstopDsRed}Ubc12^LL04684