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Originally published In Press as doi:10.1074/jbc.M609246200 on January 22, 2007

J. Biol. Chem., Vol. 282, Issue 12, 8994-9000, March 23, 2007
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Identification of a Signal Peptide for Unconventional Secretion*Formula

Edmond Dupont{ddagger}, Alain Prochiantz§, and Alain Joliot{ddagger}1

From the {ddagger}Homeoprotein Cell Biology Group and §Development and Neuropharmacology Group, CNRS UMR 8542, Ecole Normale Supérieure, 75230 Paris Cedex 05, France

Homeoproteins are a class of transcription factors defined by the structure of their DNA-binding domain, the homeodomain. In addition to their nuclear cell-autonomous activities, homeoproteins transfer between cells, thanks to two separate steps of secretion and internalization, which both rely on unconventional mechanisms. Internalization is driven by the third helix of the homeodomain (Penetratin) through a non-vesicular and endocytosis-independent mechanism. In contrast, homeoprotein secretion involves vesicular compartments and requires the presence of a sequence of 11 amino acids (Sec sequence) spanning between the second and third helix of the homeodomain. In this study, we report that the SecPen polypeptide, which combines the two identified domains, Penetratin and Sec, bears all of the necessary information to go in and out of cells. We have analyzed key mechanisms and demonstrated that this peptide can efficiently cross a tight junction epithelium.


Received for publication, September 29, 2006 , and in revised form, January 12, 2007.

* This study was supported by Centre National de la Recherche Scientifique, Ecole Normale Supérieure and grants from the Human Frontier Research Program (RGP26/2002) and the European Community Programs HPRN-CT-2001-00241 and QLK3-CT-2002-01989. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Formula The on-line version of this article (available at http://www.jbc.org) contains supplemental material.

1 To whom correspondence should be addressed: CNRS UMR8542, Ecole Normale Supérieure, 46 Rue d'Ulm, 75230 Paris Cedex 05, France. Tel.: 33-1-4432-3729; Fax: 33-1-4432-2323; E-mail: joliot{at}biologie.ens.fr.


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