Cullin-3 regulates pattern formation, external sensory organ development and cell survival during Drosophila development

Mistry, Hemlata, Wilson, Beth A, Roberts, Ian J H, O'Kane, Cahir J and Skeath, James B (2004) Cullin-3 regulates pattern formation, external sensory organ development and cell survival during Drosophila development. Mechanisms of Development, 121 (12). pp. 1495-1507. ISSN 0925-4773

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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, ß-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.

Item Type: Article
Additional Information: Supervised graduate student who is first author. Generated transgenic Drosophila used in study and recognised Cul3 alleles. Genetic and molecular demonstration that protein degradation is critical to differentiation
Schools and Departments: School of Life Sciences > Biology and Environmental Science
Depositing User: Ian Roberts
Date Deposited: 06 Feb 2012 18:10
Last Modified: 20 Mar 2012 09:25
URI: http://sro.sussex.ac.uk/id/eprint/15080
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