Discovery and Characterization of an Endogenous CXCR4 Antagonist
CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715003526 |
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doaj-6f4fd359e6c246c58166a8fdf0934801 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Onofrio Zirafi Kyeong-Ae Kim Ludger Ständker Katharina B. Mohr Daniel Sauter Anke Heigele Silvia F. Kluge Eliza Wiercinska Doreen Chudziak Rudolf Richter Barbara Moepps Peter Gierschik Virag Vas Hartmut Geiger Markus Lamla Tanja Weil Timo Burster Andreas Zgraja Francois Daubeuf Nelly Frossard Muriel Hachet-Haas Fabian Heunisch Christoph Reichetzeder Jean-Luc Galzi Javier Pérez-Castells Angeles Canales-Mayordomo Jesus Jiménez-Barbero Guillermo Giménez-Gallego Marion Schneider James Shorter Amalio Telenti Berthold Hocher Wolf-Georg Forssmann Halvard Bonig Frank Kirchhoff Jan Münch |
| spellingShingle |
Onofrio Zirafi Kyeong-Ae Kim Ludger Ständker Katharina B. Mohr Daniel Sauter Anke Heigele Silvia F. Kluge Eliza Wiercinska Doreen Chudziak Rudolf Richter Barbara Moepps Peter Gierschik Virag Vas Hartmut Geiger Markus Lamla Tanja Weil Timo Burster Andreas Zgraja Francois Daubeuf Nelly Frossard Muriel Hachet-Haas Fabian Heunisch Christoph Reichetzeder Jean-Luc Galzi Javier Pérez-Castells Angeles Canales-Mayordomo Jesus Jiménez-Barbero Guillermo Giménez-Gallego Marion Schneider James Shorter Amalio Telenti Berthold Hocher Wolf-Georg Forssmann Halvard Bonig Frank Kirchhoff Jan Münch Discovery and Characterization of an Endogenous CXCR4 Antagonist Cell Reports |
| author_facet |
Onofrio Zirafi Kyeong-Ae Kim Ludger Ständker Katharina B. Mohr Daniel Sauter Anke Heigele Silvia F. Kluge Eliza Wiercinska Doreen Chudziak Rudolf Richter Barbara Moepps Peter Gierschik Virag Vas Hartmut Geiger Markus Lamla Tanja Weil Timo Burster Andreas Zgraja Francois Daubeuf Nelly Frossard Muriel Hachet-Haas Fabian Heunisch Christoph Reichetzeder Jean-Luc Galzi Javier Pérez-Castells Angeles Canales-Mayordomo Jesus Jiménez-Barbero Guillermo Giménez-Gallego Marion Schneider James Shorter Amalio Telenti Berthold Hocher Wolf-Georg Forssmann Halvard Bonig Frank Kirchhoff Jan Münch |
| author_sort |
Onofrio Zirafi |
| title |
Discovery and Characterization of an Endogenous CXCR4 Antagonist |
| title_short |
Discovery and Characterization of an Endogenous CXCR4 Antagonist |
| title_full |
Discovery and Characterization of an Endogenous CXCR4 Antagonist |
| title_fullStr |
Discovery and Characterization of an Endogenous CXCR4 Antagonist |
| title_full_unstemmed |
Discovery and Characterization of an Endogenous CXCR4 Antagonist |
| title_sort |
discovery and characterization of an endogenous cxcr4 antagonist |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2015-05-01 |
| description |
CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation. |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124715003526 |
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doaj-6f4fd359e6c246c58166a8fdf09348012020-11-25T01:09:27ZengElsevierCell Reports2211-12472015-05-0111573774710.1016/j.celrep.2015.03.061Discovery and Characterization of an Endogenous CXCR4 AntagonistOnofrio Zirafi0Kyeong-Ae Kim1Ludger Ständker2Katharina B. Mohr3Daniel Sauter4Anke Heigele5Silvia F. Kluge6Eliza Wiercinska7Doreen Chudziak8Rudolf Richter9Barbara Moepps10Peter Gierschik11Virag Vas12Hartmut Geiger13Markus Lamla14Tanja Weil15Timo Burster16Andreas Zgraja17Francois Daubeuf18Nelly Frossard19Muriel Hachet-Haas20Fabian Heunisch21Christoph Reichetzeder22Jean-Luc Galzi23Javier Pérez-Castells24Angeles Canales-Mayordomo25Jesus Jiménez-Barbero26Guillermo Giménez-Gallego27Marion Schneider28James Shorter29Amalio Telenti30Berthold Hocher31Wolf-Georg Forssmann32Halvard Bonig33Frank Kirchhoff34Jan Münch35Institute of Molecular Virology, University of Ulm, 89081 Ulm, GermanyInstitute of Molecular Virology, University of Ulm, 89081 Ulm, GermanyInstitute of Molecular Virology, University of Ulm, 89081 Ulm, GermanyInstitute of Molecular Virology, University of Ulm, 89081 Ulm, GermanyInstitute of Molecular Virology, University of Ulm, 89081 Ulm, GermanyInstitute of Molecular Virology, University of Ulm, 89081 Ulm, GermanyInstitute of Molecular Virology, University of Ulm, 89081 Ulm, GermanyGerman Red Cross Blood Service Baden-Württemberg-Hessen and Institute for Transfusion Medicine and Immunohaematology, Goethe University, 60528 Frankfurt, GermanyGerman Red Cross Blood Service Baden-Württemberg-Hessen and Institute for Transfusion Medicine and Immunohaematology, Goethe University, 60528 Frankfurt, GermanyGerman Red Cross Blood Service Baden-Württemberg-Hessen and Institute for Transfusion Medicine and Immunohaematology, Goethe University, 60528 Frankfurt, GermanyInstitute of Pharmacology and Toxicology, University of Ulm, 89081 Ulm, GermanyInstitute of Pharmacology and Toxicology, University of Ulm, 89081 Ulm, GermanyDepartment of Dermatology and Allergic Diseases, University of Ulm, 89081 Ulm, GermanyDepartment of Dermatology and Allergic Diseases, University of Ulm, 89081 Ulm, GermanyInstitute of Organic Chemistry III, University of Ulm, 89081 Ulm, GermanyInstitute of Organic Chemistry III, University of Ulm, 89081 Ulm, GermanyDepartment of Neurosurgery, University of Ulm, 89081 Ulm, GermanyPHARIS Biotec GmbH, 30625 Hannover, GermanyUMR7200, Therapeutic Innovation Lab, CNRS-University of Strasbourg, Faculty of Pharmacy, and LabEx Medalis, 67401 Illkirch, FranceUMR7200, Therapeutic Innovation Lab, CNRS-University of Strasbourg, Faculty of Pharmacy, and LabEx Medalis, 67401 Illkirch, FranceUMR7242, Biotechnology and Cellular Signaling, School of Biotechnology of Strasbourg, 67412 Illkirch, FranceInstitute of Nutritional Science, University of Potsdam, 14558 Nuthetal-Potsdam, GermanyInstitute of Nutritional Science, University of Potsdam, 14558 Nuthetal-Potsdam, GermanyUMR7242, Biotechnology and Cellular Signaling, School of Biotechnology of Strasbourg, 67412 Illkirch, FranceDepartment of Chemistry, University San Pablo-CEU, 280040 Madrid, SpainDepartment of Physico-Chemical Biology, Centro de Investigaciones Biológicas, 28040 Madrid, SpainDepartment of Physico-Chemical Biology, Centro de Investigaciones Biológicas, 28040 Madrid, SpainDepartment of Physico-Chemical Biology, Centro de Investigaciones Biológicas, 28040 Madrid, SpainExperimental Anesthesiology Section, University Hospital Ulm, 89081 Ulm, GermanyDepartment of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USAJ. Craig Venter Institute, La Jolla, CA 92037, USAInstitute of Nutritional Science, University of Potsdam, 14558 Nuthetal-Potsdam, GermanyInstitute of Molecular Virology, University of Ulm, 89081 Ulm, GermanyGerman Red Cross Blood Service Baden-Württemberg-Hessen and Institute for Transfusion Medicine and Immunohaematology, Goethe University, 60528 Frankfurt, GermanyInstitute of Molecular Virology, University of Ulm, 89081 Ulm, GermanyInstitute of Molecular Virology, University of Ulm, 89081 Ulm, GermanyCXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.http://www.sciencedirect.com/science/article/pii/S2211124715003526 |