Drosophila cbl is essential for control of cell death and cell differentiation during eye development.
BACKGROUND
Activation of cell surface receptors transduces extracellular signals into cellular responses such as proliferation, differentiation and survival. However, as important as the activation of these receptors is their appropriate spatial and temporal down-regulation for normal development and tissue homeostasis. The Cbl family of E3-ubiquitin ligases plays a major role for the ligand-dependent inactivation of receptor tyrosine kinases (RTKs), most notably the Epidermal Growth Factor Receptor (EGFR) through ubiquitin-mediated endocytosis and lysosomal degradation.


RESULTS
Here, we report the mutant phenotypes of Drosophila cbl (D-cbl) during eye development. D-cbl mutants display overgrowth, inhibition of apoptosis, differentiation defects and increased ommatidial spacing. Using genetic interaction and molecular markers, we show that most of these phenotypes are caused by increased activity of the Drosophila EGFR. Our genetic data also indicate a critical role of ubiquitination for D-cbl function, consistent with biochemical models.


CONCLUSIONS
These data may provide a mechanistic model for the understanding of the oncogenic activity of mammalian cbl genes.
Wang
Yuan
Y
Department of Biochemistry and Molecular Biology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Werz
Christian
C
Xu
Dongbin
D
Chen
Zhihong
Z
Li
Ying
Y
Hafen
Ernst
E
Bergmann
Andreas
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D005123:Eye / Q000196:embryology*; D007150:Immunohistochemistry; D009154:Mutation; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000502:physiology*
D029721:Drosophila Proteins; D050721:Proto-Oncogene Proteins c-cbl; D066246:ErbB Receptors; C106411:Cbl protein, Drosophila