Raymond M, Gros P, Whiteway M, Thomas D Y
National Research Council of Canada, Biotechnology Research Institute, Montreal, Quebec.
Science. 1992 Apr 10;256(5054):232-4. doi: 10.1126/science.1348873.
Multidrug resistance in mammalian tumor cells is associated with the overexpression of mdr genes encoding P-glycoproteins, which function as drug efflux pumps. A yeast homolog of mdr, STE6, mediates export of a-factor mating peptide. Yeast MATa cells carrying a ste6 deletion produce no extracellular a-factor and therefore are defective in mating. Expression of a complementary DNA for the mouse mdr3 gene in a yeast ste6 deletion strain restored ability to export a-factor and to mate. A mutation (a serine to phenylalanine substitution at amino acid 939) known to affect the activity of the mdr3 gene product abolished its ability to complement the yeast ste6 deletion. Thus, functions of P-glycoproteins in normal mammalian cells may include the transmembrane export of endogenous peptides.
哺乳动物肿瘤细胞中的多药耐药性与编码P-糖蛋白的mdr基因的过表达有关，P-糖蛋白起着药物外排泵的作用。mdr的酵母同源物STE6介导α-因子交配肽的输出。携带ste6缺失的酵母MATa细胞不产生细胞外α-因子，因此在交配方面存在缺陷。在酵母ste6缺失菌株中表达小鼠mdr3基因的互补DNA可恢复输出α-因子和交配的能力。已知影响mdr3基因产物活性的一个突变（第939位氨基酸由丝氨酸替换为苯丙氨酸）消除了其互补酵母ste6缺失的能力。因此，P-糖蛋白在正常哺乳动物细胞中的功能可能包括内源性肽的跨膜输出。
