Sharma R C, Inoue S, Roitelman J, Schimke R T, Simoni R D
Department of Biological Sciences, Stanford University, California 94305-5020.
J Biol Chem. 1992 Mar 25;267(9):5731-4.
The membrane P-glycoprotein (P170) is an ATP-hydrolyzing transmembrane pump, and elevated levels of P170, due to higher expression with or without amplification of the multidrug resistance gene (mdr1), result in resistance to a variety of chemotherapeutic agents in mammalian cells. The function of the P170 pump has been proposed as a protection against toxic substances present in animal diets. Here we describe a Chinese hamster ovary cell line that was selected for resistance to a synthetic tripeptide, N-acetyl-leucyl-leucyl-norleucinal (ALLN). This ALLN-resistant variant shows the classical multidrug resistance (MDR) phenotype, including overexpression and amplification of the mdr1 gene. Additionally, a mouse embryo cell line overexpressing the transfected mdr1 gene is likewise resistant to ALLN. Our results demonstrate that P170 is capable of transporting peptides and raise the possibility that the mdr1 gene product or other MDR-like genes, present in the genome of mammalian cells, may be involved in secretion of peptides or cellular proteins as is the case with the structurally similar hylB and ste6 gene products of Escherichia coli and yeast, respectively.
膜P-糖蛋白（P170）是一种水解ATP的跨膜泵，由于多药耐药基因（mdr1）表达上调（无论是否扩增）导致P170水平升高，从而使哺乳动物细胞对多种化疗药物产生耐药性。有人提出P170泵的功能是保护机体免受动物饮食中有毒物质的侵害。在此，我们描述了一种对合成三肽N-乙酰-亮氨酰-亮氨酰-正亮氨酸（ALLN）具有抗性的中国仓鼠卵巢细胞系。这种ALLN抗性变体表现出典型的多药耐药（MDR）表型，包括mdr1基因的过表达和扩增。此外，过表达转染mdr1基因的小鼠胚胎细胞系同样对ALLN具有抗性。我们的结果表明，P170能够转运肽，并增加了一种可能性，即哺乳动物细胞基因组中存在的mdr1基因产物或其他类似MDR的基因，可能像大肠杆菌和酵母结构相似的hylB和ste6基因产物一样，参与肽或细胞蛋白的分泌。
