Localization, Regulation, and Substrate Transport Properties of Bpt1p, a Saccharomyces cerevisiae MRP-Type ABC Transporter
Localization, Regulation, and Substrate Transport Properties of Bpt1p, a Saccharomyces cerevisiae MRP-Type ABC Transporter
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DOI：
10.1128/ec.1.3.391-400.2002
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发表时间：
2002-06
期刊：
影响因子：
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通讯作者：
Kailash Gulshan;D. L. Mason;Guosheng Liu;P. A. Rea;A. Bachhawat;S. Michaelis
中科院分区：
文献类型：
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作者：
Kailash Gulshan;D. L. Mason;Guosheng Liu;P. A. Rea;A. Bachhawat;S. Michaelis
酿酒酵母Bpt1p是一种ATP结合盒（ABC）蛋白，属于MRP亚家族，与谷胱甘肽结合物转运蛋白Ycf1p同源。Bpt1p的功能以前只在体外进行了评估，通过使用非生理底物。在本研究中，我们研究了Bpt1p在体内的定位，调节和运输特性，以及其在体外运输一组原型MRP底物的能力。我们的研究结果表明，Bpt1p，像Ycf1p，定位于酵母液泡膜，在体内镉解毒和ade2色素沉着中发挥作用，并可以参与GS共轭物和葡萄糖醛酸共轭物，以及游离谷胱甘肽的运输，在体外。然而，在所有这些情况下，Bpt1p的贡献远远小于Ycf1p。此外，YCF 1和BPT 1的表达模式显著不同。而YCF 1的表达显着增加镉，腺嘌呤限制在一个ade2株，或过度表达的应激反应转录因子Yap1p，BPT 1的表达在这些条件下只受到适度的影响。因此，虽然Bpt1p和Ycf1p的功能重叠，但它们在调节和底物偏好方面的差异意味着它们以不同的方式促进细胞解毒过程。
ABSTRACT Saccharomyces cerevisiae Bpt1p is an ATP-binding cassette (ABC) protein that belongs to the MRP subfamily and is a close homologue of the glutathione conjugate (GS conjugate) transporter Ycf1p. The function of Bpt1p has previously been evaluated only in vitro, by using nonphysiological substrates. In the present study we examined the localization, regulation, and transport properties of Bpt1p in vivo, as well as its capacity to transport a set of prototypical MRP substrates in vitro. Our results show that Bpt1p, like Ycf1p, localizes to the yeast vacuolar membrane, plays a role in cadmium detoxification and ade2 pigmentation in vivo, and can participate in the transport of GS conjugates and glucuronate conjugates, as well as free glutathione, in vitro. However, in all of these cases the contribution of Bpt1p is substantially less than that of Ycf1p. In addition, the expression patterns of YCF1 and BPT1 differ significantly. Whereas YCF1 expression is markedly increased by cadmium, adenine limitation in an ade2 strain, or overexpression of the stress-responsive transcription factor Yap1p, BPT1 expression is only modestly affected under these conditions. Thus, although the functional capabilities of Bpt1p and Ycf1p overlap, their differences in regulation and substrate preference imply that they contribute to cellular detoxification processes in different ways.