Discovery and Characterization of an Endogenous CXCR4 Antagonist

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dc.contributor.advisorTimo, Burster
dc.contributor.authorO., Zirafi
dc.contributor.authorK-A., Kim
dc.contributor.authorL., Ständker
dc.contributor.authorK. B., Mohr
dc.contributor.authorD., Sauter
dc.contributor.authorA., Heigele
dc.contributor.authorS. F., Kluge
dc.contributor.authorE., Wiercinska
dc.contributor.authorD., Chudziak
dc.contributor.authorR., Richter
dc.contributor.authorB., Moepps
dc.contributor.authorP., Gierschik
dc.contributor.authorV., Vas
dc.contributor.authorH., Geiger
dc.contributor.authorM., Lamla
dc.contributor.authorT., Weil
dc.contributor.authorT., Burster
dc.contributor.authorA., Zgraja
dc.contributor.authorF., Daubeuf
dc.contributor.authorN., Frossard
dc.contributor.authorTimo, Burster
dc.date.accessioned2018-08-20T09:13:59Z
dc.date.available2018-08-20T09:13:59Z
dc.date.issued2015-05-05
dc.description.abstractCXCL12-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 EPIX4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.en_US
dc.identifier.citationZirafi, O. , Kim, K-A. , Ständker, L. , Mohr, K. B. , Sauter, D. , Heigele, A. , Kluge, S. F. , Wiercinska, E. , Chudziak, D. , Richter, R. , Moepps, B. , Gierschik, P. , Vas, V. , Geiger, H. , Lamla, M. , Weil, T. , Burster, T. , Zgraja, A. , Daubeuf, F. , Frossard, N. 2015. Discovery and Characterization of an Endogenous CXCR4 Antagonist. Cell Reports. 11, 5, p. 737-47 11 p.en_US
dc.identifier.urihttp://nur.nu.edu.kz/handle/123456789/3392
dc.language.isoenen_US
dc.publisherCell Reportsen_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.titleDiscovery and Characterization of an Endogenous CXCR4 Antagonisten_US
dc.typeArticleen_US
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