A look at life from the homeodomain

Introduction This workshop brought together developmental biologists and oncologists for three intense days of discussions about the recent progress that has been made on the roles of homeodomain proteins in development, haematopoiesis and leukaemogenesis. The homeo-domain is a 61-amino-acid DNA-binding motif with specific sequence and structural characteristics (Gehring & Hiromi, 1986). Homeodomain proteins were initially identified in Drosophila as being responsible, when mutated, for homeotic transformations—that is, the conversion of a part of the body into the likeness of another. Since their initial discovery, the number of homeodomain proteins has increased enormously, and they comprise several different families of transcription factors. The main stars of the meeting were members of the Hox family and of the three amino-acid loop extension (TALE) families, with some other homeodomain proteins making guest appearances. TALE proteins include the PBC family (Exd in Drosophila and Pbx proteins in vertebrates) and the Hth/Meis superfamily (Hth in Drosophila, and Meis and Prep proteins in vertebrates). The link between Hox and TALE proteins is their functional interactions, which were initially revealed in flies by genetic analyses and later supported by biochemical data (Mann & Affolter, 1998; Moens & Selleri, 2006). PBC proteins have been shown to act as Hox cofactors that mainly determine Hox DNA-binding specificity and selectivity. Hth/Meis proteins interact with PBC proteins, participating in ternary complexes with Hox proteins, or modulating PBC protein stability and subcellular localization.