[Protein transduction, from technology to physiology].
In the early 90s, we found that the DNA-binding domain (homeodomain) of Antennapedia, a homeoprotein transcription factor, was internalized by live cells gaining access to their cytoplasm and nuclei. It was soon revealed that internalization is due to the third helix of the homeodomain, composed of sixteen amino acids. This short peptide baptized Penetratin is the first of a large series of transduction peptides widely used for the internalization of all sorts of cargoes in vitro and in vivo. Although transduction peptides are being developed with the latter practical goal, the most intriguing outcome of our initial observation is that full-length homeoproteins are transferred between cells and have non-cell autonomous transcriptional and translational activities. This new signaling mechanism requires that homeoproteins be internalized and secreted. Secretion is Golgi independent and requires a small sequence also present in the homeodomain but distinct from the Penetratin sequence. The consequences of this novel signaling mechanism are briefly discussed.
Prochiantz
Alain
A
CNRS UMR 8542, Ecole normale supérieure, 46, rue d'Ulm, 75230 Paris Cedex 05, France. Alain.Prochiantz@ens.fr
D021581:Active Transport, Cell Nucleus; D000818:Animals; D051943:Antennapedia Homeodomain Protein / Q000737:chemistry / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology*; D057846:Cell-Penetrating Peptides; D019143:Evolution, Molecular; D015696:Gene Products, tat / Q000737:chemistry / Q000502:physiology; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015398:Signal Transduction; D014158:Transcription, Genetic
D051943:Antennapedia Homeodomain Protein; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D015696:Gene Products, tat; D018398:Homeodomain Proteins; C414409:penetratin