Reference Report

Reference
Citation	Mistry, H., Wilson, B.A., Roberts, I.J., O'Kane, C.J., Skeath, J.B. (2004). Cullin-3 regulates pattern formation, external sensory organ development and cell survival during Drosophila development. Mech. Dev. 121(12): 1495--1507. (Export to RIS)
FlyBase ID	FBrf0180486
Publication Type	Research paper
PubMed ID	15511641
PubMed Abstract	Ubiquitin-mediated proteolysis regulates the steady-state abundance of proteins and controls cellular homoeostasis by abrupt elimination of key effector proteins. A multienzyme system targets proteins for destruction through the covalent attachment of a multiubiquitin chain. The specificity and timing of protein ubiquitination is controlled by ubiquitin ligases, such as the Skp1-Cullin-F box protein complex. Cullins are major components of SCF complexes, and have been implicated in degradation of key regulatory molecules including Cyclin E, beta-catenin and Cubitus interruptus. Here, we describe the genetic identification and molecular characterisation of the Drosophila Cullin-3 homologue. Perturbation of Cullin-3 function has pleiotropic effects during development, including defects in external sensory organ development, pattern formation and cell growth and survival. Loss or overexpression of Cullin-3 causes an increase or decrease, respectively, in external sensory organ formation, implicating Cullin-3 function in regulating the commitment of cells to the neural fate. We also find that Cullin-3 function modulates Hedgehog signalling by regulating the stability of full-length Cubitus interruptus (Ci155). Loss of Cullin-3 function in eye discs but not other imaginal discs promotes cell-autonomous accumulation of Ci155. Conversely, overexpression of Cullin-3 results in a cell-autonomous stabilisation of Ci155 in wing, haltere and leg, but not eye, imaginal discs suggesting tissue-specific regulation of Cullin-3 function. The diverse nature of Cullin-3 phenotypes highlights the importance of targeted proteolysis during Drosophila development.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Mech. Dev.
Title	Mechanisms of Development
Publication Year	1990-
ISBN/ISSN	0925-4773
Data from Reference
Aberrations (5)
	Df(2L)osp29 Df(2L)TE35D-15 Df(2L)wg-CX3 Df(3L)vin7 T(Y;2)TE35B-18
Alleles (18)
	Avic\GFP^Scer\UAS.cUa Cul-3⁰⁶⁴³⁰ Cul-3^d577 Cul-3^gft1 Cul-3^gft2 Cul-3^gft4 Cul-3^gft6 Cul-3^GR18 Cul-3^Scer\UAS.cMa Cul-3^ΔC.Scer\UAS Ecol\lacZ^neur-A101 Gli³ Gαs^{Q215L.Scer\UAS} Scer\GAL4^dpp.blk1 Scer\GAL4^en-e16E Scer\GAL4^OK10 Scer\GAL4^sca-4512 w^+mC
Constructs (5)
	P{GAL4-dpp.blk1} P{UAS-GFP.U} P{UAS-gft.FL} P{UAS-gft.ΔC} P{UAS-G-sα60A.Q215L}
Genes (11)
	ac Avic\GFP ci ct Cul-3 Ecol\lacZ Gli Gαs neur Scer\GAL4 w
Insertions (5)
	P{en2.4-GAL4}e16E P{GAL4}sca⁴⁵¹² P{GawB}OK10 P{lArB}neur^A101 P{PZ}Cul-3⁰⁶⁴³⁰