Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen.
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.
Frye
Björn C
BC
Department of Nephrology & Immunology, University Hospital RWTH Aachen, Aachen, Germany.
Halfter
Sarah
S
Djudjaj
Sonja
S
Muehlenberg
Philipp
P
Weber
Susanne
S
Raffetseder
Ute
U
En-Nia
Abdelaziz
A
Knott
Hanna
H
Baron
Jens M
JM
Dooley
Steven
S
Bernhagen
Jürgen
J
Mertens
Peter R
PR
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*
D008070:Lipopolysaccharides; D008934:Mitogens; D051840:Y-Box-Binding Protein 1