Regulation of LIM homeodomain activity in vivo: a tetramer of dLDB and apterous confers activity and capacity for regulation by dLMO.
Dorsal-ventral axis formation in the Drosophila wing depends on the activity of the LIM homeodomain transcription factor Apterous and its cofactor, dLDB/Chip. We present evidence that Apterous activity depends on the formation of a LIM homeodomain dimer bridged by a dimer of cofactor. We show that Apterous activity levels are regulated in vivo by dLMO, an antagonist of homodimer formation. Making use of a constitutively active form of Apterous and dominant-negative forms of Apterous and dLDB/Chip, we show that the normal function of dLMO is to downregulate Apterous activity and that the dLMO mutant phenotype is due to excess Apterous activity. These findings may point to a general mechanism for regulation of LIM homeodomain protein activity.
Milán
M
M
European Molecular Biology Laboratory, Heidelberg, Germany.
Cohen
S M
SM
D000818:Animals; D019521:Body Patterning; D003001:Cloning, Molecular; D019281:Dimerization; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development*; D029721:Drosophila Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D019476:Insect Proteins / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000254:growth & development*
C096249:Bx protein, Drosophila; C108740:Chi protein, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D060850:LIM-Homeodomain Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C074459:ap protein, Drosophila