Homeodomain-derived peptides. In and out of the cells.
The internalization of homeodomains and of homeopeptides derived from the third helix of the homeodomain of Antennapedia, a Drosophila transcription factor, is used by some investigators to target exogenous hydrophilic compounds into live cells. In addition to this very practical aspect of drug delivery, translocation across biologic membranes of peptides subsequently addressed to the cell cytoplasm and nucleus raises several questions. A first series of questions pertains to the mechanism of translocation. Thanks to the synthesis of several peptides derived from the third helix of the Antennapedia homeodomain, we began to investigate the mechanism of translocation and we have shown that it is not dependent upon the presence of a chiral receptor and probably involves the formation of inverted micelles. A second series of questions is related to the physiologic significance of the phenomenon. In a first approach, we demonstrated that some full-length homeoproteins are internalized and secreted in vitro. The mechanism of internalization is probably similar to that of the homeodomain or of its third helix, but secretion involves a different mechanism which requires an association with specialized intracellular membranous structures. The existence of specific mechanisms for homeoprotein internalization and secretion suggests that this class of transcription factors may have important signaling properties.
Prochiantz
A
A
Ecole Normale Supérieure, CNRS UMR 8542, Paris, France. prochian@wotan.ens.fr
D000595:Amino Acid Sequence; D051943:Antennapedia Homeodomain Protein; D001692:Biological Transport; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D008823:Micelles; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors
D051943:Antennapedia Homeodomain Protein; D018398:Homeodomain Proteins; D008823:Micelles; D009687:Nuclear Proteins; D010446:Peptide Fragments; D014157:Transcription Factors