DOI: 10.1111/j.1749-6632.1999.tb09410.x. Homeodomain‐Derived Peptides: In and Out of the Cells

Homeodomain‐Derived Peptides: In and Out of the Cells

10.1111/j.1749-6632.1999.tb09410.x

Crossref journal-article

Wiley

Annals of the New York Academy of Sciences (311)

Abstract

Abstract: 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.

Bibliography

PROCHIANTZ, A. (1999). HomeodomainâDerived Peptides: In and Out of the Cells. Annals of the New York Academy of Sciences, 886(1), 172â179. Portico.

Authors 1

ALAIN PROCHIANTZ (first)

References 40 Referenced 48

10.1016/0092-8674(94)90290-9
10.1016/0092-8674(94)90292-5
10.1016/0168-9525(96)81383-7
{'key': 'e_1_2_10_5_2', 'first-page': '435', 'article-title': 'The engrailed genes: Evolution of function', 'volume': '2', 'author': 'Joyner A.L.', 'year': '1991', 'journal-title': 'Semin. Dev. Biol.'} / Semin. Dev. Biol. / The engrailed genes: Evolution of function by Joyner A.L. (1991)
10.1016/0166-2236(88)90154-3
10.1038/333376a0
10.1016/0092-8674(92)90406-3
{'key': 'e_1_2_10_9_2', 'first-page': '841', 'article-title': 'C', 'volume': '355', 'author': 'Miller D.M.', 'year': '1992', 'journal-title': 'elegans unc-4 genes encode a homeoprotein that determines the pattern of synaptic input to specific motor neurons. Nature'} / elegans unc-4 genes encode a homeoprotein that determines the pattern of synaptic input to specific motor neurons. Nature / C by Miller D.M. (1992)
10.1242/dev.125.2.279 / Development / Increased apoptosis of motoneurons and altered somatotopic maps in the brachial spinal cord of Hoxc‐8‐deficient mice by Tiret L. (1998)
10.1038/355838a0
10.1016/0896-6273(90)90206-U
10.1016/0896-6273(89)90233-X / Neuron / Ras p21 protein promotes survival and fiber outgrowth of cultured embryonics neurons by Borasio G.D. (1989)
10.1073/pnas.88.5.1864
10.1083/jcb.120.2.485
{'key': 'e_1_2_10_16_2', 'first-page': '1121', 'article-title': 'α‐2,8‐Polysialic acid is the neuronal surface receptor of Antennapedia homeobox peptide', 'volume': '3', 'author': 'Joliot A. H.', 'year': '1991', 'journal-title': 'New Biol.'} / New Biol. / α‐2,8‐Polysialic acid is the neuronal surface receptor of Antennapedia homeobox peptide by Joliot A. H. (1991)
10.1073/pnas.90.19.9120
10.1016/0014-5793(95)00681-X
10.1016/S0021-9258(17)34080-2 / J. Biol. Chem. / The third helix of Antennapedia homeodomain translocates through biological membranes by Derossi D. (1994)
10.1074/jbc.271.30.18188
10.1016/S0962-8924(98)80017-2
10.1111/j.1432-1033.1996.0372r.x
Dekruijff B. P.R. Cullis A.J. Verkleij M.J. Hope C.J.A. Vanechteld T.F. Taraschi P. Vanhoogevest J.A. Killian A. Rietvel & A.T.M. Vandersteen. 1985. Modulation of lipid polymorphism by lipid‐protein interactions.InProgress in Protein‐Lipid Interactions: 89–142. Elsevier Science Publishers B.V. Netherlands.
10.1016/S0959-4388(96)80095-X
10.1016/S0960-9822(02)00544-4
10.1074/jbc.272.35.22349
10.1016/S0960-9822(02)00425-6
10.4049/jimmunol.157.2.650 / J. Immunol. / Introduction of exogenous antigen into the MHC Class I processing and presentation pathway by Drosophila Antennapedia homeodomain primes cytotoxic T cells in vivo by Schutze‐Redelmeier M.P. (1996)
10.1038/nbt0998-857
10.1016/0925-4773(95)00478-5
10.1242/dev.124.10.1865 / Development / Association of engrailed homeoproteins with vesicles presenting caveolae‐like properties by Joliot A. (1997)
10.1016/S0960-9822(07)00346-6
10.1002/bies.950170109
10.1073/pnas.93.4.1677
10.1016/0076-6879(93)25043-2
10.1242/dev.111.2.287
10.1046/j.1523-1747.1999.00703.x
10.1002/j.1460-2075.1993.tb05733.x
10.1016/S0092-8674(00)81843-7
10.1038/373721a0
10.1074/jbc.272.25.16010

Dates

Type	When
Created	19 years, 7 months ago (Feb. 6, 2006, 11:43 a.m.)
Deposited	1 year, 11 months ago (Sept. 25, 2023, 1:38 p.m.)
Indexed	4 months, 4 weeks ago (April 10, 2025, 5:50 a.m.)
Issued	25 years, 9 months ago (Dec. 1, 1999)
Published	25 years, 9 months ago (Dec. 1, 1999)
Published Online	19 years, 7 months ago (Feb. 6, 2006)
Published Print	25 years, 9 months ago (Dec. 1, 1999)

Funders 0

None

BibTeX

@article{PROCHIANTZ_1999, title={Homeodomain‐Derived Peptides: In and Out of the Cells}, volume={886}, ISSN={1749-6632}, url={http://dx.doi.org/10.1111/j.1749-6632.1999.tb09410.x}, DOI={10.1111/j.1749-6632.1999.tb09410.x}, number={1}, journal={Annals of the New York Academy of Sciences}, publisher={Wiley}, author={PROCHIANTZ, ALAIN}, year={1999}, month=dec, pages={172–179} }

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