Drosophila cbl is essential for control of cell death and cell differentiation during eye development

PloS One
Yuan WangAndreas Bergmann

Abstract

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. 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. These data may provide a mechanistic model for the understanding of the oncogenic activity of mammalian cbl genes.

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Citations

Jun 6, 2009·Cell Death and Differentiation·A Bergmann
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hon-Ren HuangTom Maniatis
Sep 29, 2012·Cell Death and Differentiation·A E ChristiansenA Bergmann
Oct 23, 2012·Biochimica Et Biophysica Acta·Bhopal MohapatraHamid Band
Jul 8, 2003·BMC Developmental Biology·Jamie M KramerBrian E Staveley
Jul 11, 2012·Molecular and Cellular Biology·Yue YuYong Liu

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Methods Mentioned

BETA
ubiquitination

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