Beadex encodes an LMO protein that regulates Apterous LIM-homeodomain activity in Drosophila wing development: a model for LMO oncogene function.
Formation of the dorsal-ventral axis of the Drosophila wing depends on activity of the LIM-homeodomain protein Apterous (Ap). Here we report that Ap activity levels are modulated by dLMO, the protein encoded by the Beadex (Bx) gene. Overexpression of dLMO in Bx mutants interferes with Apterous function. Conversely, Bx loss-of-function mutants fail to down-regulate Apterous activity at late stages of wing development. Biochemical analysis shows that dLMO protein competes for binding of Apterous to its cofactor Chip. These data suggest that Apterous activity depends on formation of a functional complex with Chip and that the relative levels of dLMO, Apterous, and Chip determine the level of Apterous activity. The dominant interference mechanism of dLMO action may serve as a model for the mechanism by which LMO oncogenes cause cancer when misexpressed in T cells.
Milán
M
M
European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Diaz-Benjumea
F J
FJ
Cohen
S M
SM
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development* / Q000502:physiology; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology*; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000502:physiology; D060850:LIM-Homeodomain Proteins; D046911:Macromolecular Substances; D008954:Models, Biological; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000502:physiology; D009857:Oncogenes; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology*; D014921:Wings, Animal / Q000254:growth & development
C096249:Bx protein, Drosophila; C108740:Chi protein, Drosophila; D017931:DNA Primers; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D060850:LIM-Homeodomain Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D014157:Transcription Factors; C074459:ap protein, Drosophila