title: Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen.
abstract: Y-box protein (YB)-1 of the cold-shock protein family functions in gene transcription and RNA processing. Extracellular functions have not been reported, but the YB-1 staining pattern in inflammatory glomerular diseases, without adherence to cell boundaries, suggests an extracellular occurrence. Here, we show the secretion of YB-1 by mesangial and monocytic cells after inflammatory challenges. It should be noted that YB-1 was secreted through a non-classical mode resembling that of the macrophage migration inhibitory factor. YB-1 release requires ATP-binding cassette transporters, and microvesicles protect YB-1 from protease degradation. Two lysine residues in the YB-1 carboxy-terminal domain are crucial for its release, probably because of post-translational modifications. The addition of purified recombinant YB-1 protein to different cell types results in increased DNA synthesis, cell proliferation and migration. Thus, the non-classically secreted YB-1 has extracellular functions and exerts mitogenic as well as promigratory effects in inflammation.
authors.affiliation: Department of Nephrology & Immunology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Björn C
authors.initials: BC
authors.lastname: Frye
authors.forename: Sarah
authors.initials: S
authors.lastname: Halfter
authors.forename: Sonja
authors.initials: S
authors.lastname: Djudjaj
authors.forename: Philipp
authors.initials: P
authors.lastname: Muehlenberg
authors.forename: Susanne
authors.initials: S
authors.lastname: Weber
authors.forename: Ute
authors.initials: U
authors.lastname: Raffetseder
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: En-Nia
authors.forename: Hanna
authors.initials: H
authors.lastname: Knott
authors.forename: Jens M
authors.initials: JM
authors.lastname: Baron
authors.forename: Steven
authors.initials: S
authors.lastname: Dooley
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bernhagen
authors.forename: Peter R
authors.initials: PR
authors.lastname: Mertens
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008934:Mitogens / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055571:Secretory Pathway / Q000187:drug effects; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D008934:Mitogens; D051840:Y-Box-Binding Protein 1