TY - JOUR
T1 - Cullin-3 regulates pattern formation, external sensory organ development and cell survival during Drosophila development
AU - Mistry, Hemlata
AU - Wilson, Beth A.
AU - Roberts, Ian J.H.
AU - O'Kane, Cahir J.
AU - Skeath, James B.
N1 - Funding Information:
We are indebted to the Bloomington and Umeå Stock Centers for the Deficiency Kit. We thank The Developmental Studies Hybridoma Bank for antisera. We thank Eva-Marie Wormstall, Nancy Myers, and Ted Hansen for help in raising dCul-3 antisera. We are grateful for insightful discussions with members of the Skeath lab. We thank José de Celis, Joan Hooper, Petra Levin, Teresa Orenic and Tanya Wolff for critical comments on the manuscript. HM was supported by a Wellcome Trust Prize Studentship in the laboratory of CO'K. This work was supported by grants from The Pharmacia-Washington University Biomedical Program and the National Institutes of Neurological Disorders and Stroke (NINDS NS36570) to JBS.
PY - 2004/12
Y1 - 2004/12
N2 - 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, β-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.
AB - 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, β-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.
KW - Ci stability
KW - Cullin
KW - Drosophila wing development
KW - Protein degradation
KW - SCF
UR - http://www.scopus.com/inward/record.url?scp=7044272794&partnerID=8YFLogxK
U2 - 10.1016/j.mod.2004.07.007
DO - 10.1016/j.mod.2004.07.007
M3 - Article
C2 - 15511641
AN - SCOPUS:7044272794
SN - 0925-4773
VL - 121
SP - 1495
EP - 1507
JO - Mechanisms of Development
JF - Mechanisms of Development
IS - 12
ER -