Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005, USA- bondos@rice-edu
Abstract: Positional information provided by Hox homeotic transcription factors is integrated with other transcription factors and cell signaling cascades in specific combinations to dictate context- and gene-specific Hox activity- Protein-protein interactions between these groups have long been hypothesized to modulate Hox functions, yielding a context-specific function- However, difficulties in applying interaction screens to potent transcription factors have limited partner identification- A yeast two-hybrid screen using transcription activation-deficient mutants of the Drosophila melanogaster Hox protein Ultrabithorax IB identified an array of interacting proteins, consisting primarily of transcription factors and components of cell signaling pathways- Interactions were confirmed with wild-type Ultrabithorax -UBX- in phage display experiments and by immunoprecipitation for a subset of partners- In vivo assays demonstrated that two Ultrabithorax IB partners, Armadillo, regulated by Wingless-WNT signaling, and the homeodomain protein Aristaless, inhibit UBX-dependent haltere development from the default wing development pathway- Therefore, transcription factors and cell signaling proteins that subdivide Hox-specified tissues can both alter Hox function in vivo and interact with the corresponding Hox protein in vitro- UBX may also modulate partner function- the pupal death phenotype induced by ectopic expression of the UBX partner Hairy required the presence of UBX- Thus, Hox-transcription factor complexes may integrate a variety of positional cues, generating the specificity and versatility required for context-dependent Hox function-