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Y‐box protein‐1 is actively secreted through a non‐classical pathway and acts as an extracellular mitogen
Author(s) -
Frye Björn C,
Halfter Sarah,
Djudjaj Sonja,
Muehlenberg Philipp,
Weber Susanne,
Raffetseder Ute,
EnNia Abdelaziz,
Knott Hanna,
Baron Jens M,
Dooley Steven,
Bernhagen Jürgen,
Mertens Peter R
Publication year - 2009
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2009.81
Subject(s) - extracellular , microbiology and biotechnology , microvesicles , secretion , biology , mesangial cell , biochemistry , gene , in vitro , microrna
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.