Efficient intracellular delivery of GFP by homeodomains of Drosophila Fushi-tarazu and engrailed proteins

The 60 amino acid long homeodomain of Antennapedia (Antp), either alone or as a fusion protein with 30-40 amino acid long foreign polypeptides, has be en reported to cross biological membranes by an energy- and receptor-protei n-independent mechanism. Moreover, the 16 amino acid long third helix of th e Antp homeodomain, so-called penetratin, possesses translocation propertie s when fused to fewer than 100 amino acids as well. These findings led us t o study whether such a protein tansduction property is shared by other home odomains. We report here that homeodomains of two homeoproteins, Fushi-tara zu and Engrailed, are able to transduce a 238 amino acid long green fluores cent protein into cultured cells as efficiently as other well-known protein transduction domains, such as an internal oligopeptide of Tat and penetrat in. These findings suggest that such transduction activity of homeodomains might have some physiological roles and that it can be exploited for develo pment of efficient transduction vectors for research use and protein therap y.