Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen.
Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen.
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DOI：
10.1038/embor.2009.81
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发表时间：
2009-07
期刊：
影响因子：
7.7
通讯作者：
Mertens, Peter R.
中科院分区：
文献类型：
--
作者：
Frye, Bjoern C.;Halfter, Sarah;Djudjaj, Sonja;Muehlenberg, Philipp;Weber, Susanne;Raffetseder, Ute;En-Nia, Abdelaziz;Knott, Hanna;Baron, Jens M.;Dooley, Steven;Bernhagen, Juergen;Mertens, Peter R.
Y-box蛋白（YB）-1属于冷休克蛋白家族，在基因转录和RNA加工中发挥重要作用。细胞外功能尚未报道，但在炎性肾小球疾病中的YB-1染色模式，不粘附细胞边界，表明细胞外发生。在这里，我们显示了炎症刺激后系膜细胞和单核细胞分泌YB-1。应该注意的是，YB-1通过类似于巨噬细胞移动抑制因子的非经典模式分泌。YB-1的释放需要ATP结合盒转运体，微泡保护YB-1免受蛋白酶降解。YB-1羧基末端结构域中的两个赖氨酸残基对其释放至关重要，可能是因为翻译后修饰。将纯化的重组YB-1蛋白添加到不同类型的细胞中导致DNA合成、细胞增殖和迁移增加。因此，非经典分泌的YB-1具有细胞外功能，并在炎症中发挥促有丝分裂和促迁移作用。
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.
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