Department of Biochemistry, University of Wisconsin—Madison, Madison, Wisconsin 53706, United States.
Biochemistry. 2010 Dec 21;49(50):10666-73. doi: 10.1021/bi1013485. Epub 2010 Nov 23.
Bovine pancreatic ribonuclease (RNase A) can enter human cells, even though it lacks a cognate cell-surface receptor protein. Here, we report on the biochemical basis for its cellular uptake. Analyses in vitro and in cellulo revealed that RNase A interacts tightly with abundant cell-surface proteoglycans containing glycosaminoglycans, such as heparan sulfate and chondroitin sulfate, as well as with sialic acid-containing glycoproteins. The uptake of RNase A correlates with cell anionicity, as quantified by measuring electrophoretic mobility. The cellular binding and uptake of RNase A contrast with those of Onconase, an amphibian homologue that does not interact tightly with anionic cell-surface glycans. As anionic glycans are especially abundant on human tumor cells, our data predicate utility for mammalian ribonucleases as cancer chemotherapeutic agents.
牛胰腺核糖核酸酶（RNase A）可以进入人体细胞，尽管它缺乏同源的细胞表面受体蛋白。在这里，我们报告其细胞摄取的生化基础。体外和体内分析表明，RNase A 与含有糖胺聚糖的丰富的细胞表面蛋白聚糖（如肝素硫酸盐和软骨素硫酸盐）以及含有唾液酸的糖蛋白紧密相互作用。RNase A 的摄取与细胞阴离子性相关，如通过测量电泳迁移率来定量。RNase A 的细胞结合和摄取与蛙类同源物 Onconase 的结合和摄取形成对比，Onconase 与阴离子细胞表面糖链的结合不紧密。由于阴离子糖链在人肿瘤细胞上特别丰富，我们的数据预示着哺乳动物核糖核酸酶作为癌症化学治疗剂的应用。
