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首页> 外文期刊>Molecular and Cellular Biology >Regulation of the Extrinsic Apoptotic Pathway by the Extracellular Matrix Glycoprotein EMILIN2
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Regulation of the Extrinsic Apoptotic Pathway by the Extracellular Matrix Glycoprotein EMILIN2

机译：细胞外基质糖蛋白EMILIN2对细胞外凋亡途径的调节

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摘要

Elastin microfibril interface-located proteins (EMILINs) constitute a family of extracellular matrix (ECM) glycoproteins characterized by the presence of an EMI domain at the N terminus and a gC1q domain at the C terminus. EMILIN1, the archetype molecule of the family, is involved in elastogenesis and hypertension etiology, whereas the function of EMILIN2 has not been resolved. Here, we provide evidence that the expression of EMILIN2 triggers the apoptosis of different cell lines. Cell death depends on the activation of the extrinsic apoptotic pathway following EMILIN2 binding to the TRAIL receptors DR4 and, to a lesser extent, DR5. Binding is followed by receptor clustering, colocalization with lipid rafts, death-inducing signaling complex assembly, and caspase activation. The direct activation of death receptors by an ECM molecule that mimics the activity of the known death receptor ligands is novel. The knockdown of EMILIN2 increases transformed cell survival, and overexpression impairs clonogenicity in soft agar and three-dimensional growth in natural matrices due to massive apoptosis. These data demonstrate an unexpected direct and functional interaction of an ECM constituent with death receptors and discloses an additional mechanism by which ECM cues can negatively affect cell survival.
机译：弹性蛋白微纤维定位的蛋白质（EMILINs）构成了一系列细胞外基质（ECM）糖蛋白，其特征是在N端存在EMI域，在C端存在gC1q域。 EMILIN1是该家族的原型分子，参与了弹性发生和高血压病因学，而EMILIN2的功能尚未得到解决。在这里，我们提供证据表明EMILIN2的表达触发了不同细胞系的凋亡。细胞死亡取决于EMILIN2与TRAIL受体DR4以及较小程度上与DR5结合后外部细胞凋亡途径的激活。结合之后是受体簇集，与脂质筏的共定位，诱导死亡的信号复合物组装以及胱天蛋白酶的活化。通过模仿已知死亡受体配体活性的ECM分子直接激活死亡受体是新颖的。敲低EMILIN2可以提高转化细胞的存活率，并且由于大量的细胞凋亡，过表达会损害软琼脂的克隆形成能力和天然基质的三维生长。这些数据证明了ECM成分与死亡受体之间意想不到的直接和功能性相互作用，并公开了ECM提示可对细胞存活产生负面影响的其他机制。

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