生物
细胞生物学
分泌物
细胞保护
半胱氨酸蛋白酶1
促炎细胞因子
半胱氨酸蛋白酶
内质网
先天免疫系统
炎症
炎症体
细胞凋亡
免疫学
生物化学
免疫系统
程序性细胞死亡
作者
Martin Keller,Andreas Rüegg,Sabine Werner,Hans‐Dietmar Beer
出处
期刊:Cell
[Elsevier]
日期:2008-03-01
卷期号:132 (5): 818-831
被引量:824
标识
DOI:10.1016/j.cell.2007.12.040
摘要
Mammalian cells export most proteins by the endoplasmic reticulum/Golgi-dependent pathway. However, some proteins are secreted via unconventional, poorly understood mechanisms. The latter include the proinflammatory cytokines interleukin(IL)-1β, IL-18, and IL-33, which require activation by caspase-1 for biological activity. Caspase-1 itself is activated by innate immune complexes, the inflammasomes. Here we show that secretion of the leaderless proteins proIL-1α, caspase-1, and fibroblast growth factor (FGF)-2 depends on caspase-1 activity. Although proIL-1α and FGF-2 are not substrates of the protease, we demonstrated their physical interaction. Secretome analysis using iTRAQ proteomics revealed caspase-1-mediated secretion of other leaderless proteins with known or unknown extracellular functions. Strikingly, many of these proteins are involved in inflammation, cytoprotection, or tissue repair. These results provide evidence for an important role of caspase-1 in unconventional protein secretion. By this mechanism, stress-induced activation of caspase-1 directly links inflammation to cytoprotection, cell survival, and regenerative processes.
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