Reference Report

Reference
Citation	Lai, E.C., Roegiers, F., Qin, X., Jan, Y.N., Rubin, G.M. (2005). The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta. Development 132(10): 2319--2332. (Export to RIS)
FlyBase ID	FBrf0187469
Publication Type	Research paper
PubMed ID	15829515
PubMed Abstract	The receptor Notch and its ligands of the Delta/Serrate/LAG2 (DSL) family are the central components in the Notch pathway, a fundamental cell signaling system that regulates pattern formation during animal development. Delta is directly ubiquitinated by Drosophila and Xenopus Neuralized, and by zebrafish Mind bomb, two unrelated RING-type E3 ubiquitin ligases with common abilities to promote Delta endocytosis and signaling activity. Although orthologs of both Neuralized and Mind bomb are found in most metazoan organisms, their relative contributions to Notch signaling in any single organism have not yet been assessed. We show here that a Drosophila ortholog of Mind bomb (D-mib) is a positive component of Notch signaling that is required for multiple Neuralized-independent, Notch-dependent developmental processes. Furthermore, we show that D-mib associates physically and functionally with both Serrate and Delta. We find that D-mib uses its ubiquitin ligase activity to promote DSL ligand activity, an activity that is correlated with its ability to induce the endocytosis and degradation of both Delta and Serrate (see also Le Borgne et al., 2005). We further demonstrate that D-mib can functionally replace Neuralized in multiple cell fate decisions that absolutely require endogenous Neuralized, a testament to the highly similar activities of these two unrelated ubiquitin ligases in regulating Notch signaling. We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophila development.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Development
Title	Development
Publication Year	1987-
ISBN/ISSN	0950-1991
Data from Reference
Alleles (20)
	Avic\GFP^Scer\UAS.cUa Dl^hs.PS Dl^Scer\UAS.cDa mib1^{C.Scer\UAS.T:Zzzz\His6,T:Hsap\MYC} mib1^EY97600 mib1^{N.Scer\UAS.T:Zzzz\His6,T:Hsap\MYC} mib1^{Scer\UAS.T:Zzzz\His6,T:Hsap\MYC} mib1^{Δ3RF.Scer\UAS.T:Zzzz\His6,T:Hsap\MYC} mib1^{ΔRF.Scer\UAS.T:Zzzz\His6,T:Hsap\MYC} neur¹¹ neur^A101 neur^Scer\UAS.cLa neur^{αRING.Scer\UAS} pon^{LD.Scer\UAS.T:Avic\GFP} Scer\GAL4^Bx-MS1096 Scer\GAL4^dpp.blk1 Scer\GAL4^ey.PS Scer\GAL4^GMR.PF Scer\GAL4^sca-537.4 Ser^Scer\UAS.cSa
Constructs (15)
	P{ey-GAL4.S} P{GAL4-dpp.blk1} P{GAL4-ninaE.GMR} P{hsp70-Dl.S} P{UAS-Dl.D} P{UAS-GFP.U} P{UAS-mib1.C} P{UAS-mib1.His6.MYC} P{UAS-mib1.N} P{UAS-mib1.Δ3RF} P{UAS-mib1.ΔRF} P{UAS-neur.L} P{UAS-neur.αRING} P{UAS-pon.GFP.LD} P{UAS-Ser.mg5603}
Genes (17)
	Avic\GFP ct Dl elav mib1 mib2 N neur nub pon Scer\GAL4 sens Ser Su(H) T:Avic\GFP T:Hsap\MYC T:Zzzz\His6
Insertions (4)
	P{EPgy2}mib1^EY97600 P{GawB}Bx^MS1096 P{GawB}sca^537.4 P{lArB}neur^A101
Natural transposons (1)
	P-element