Yeast Bax inhibitor, Bxi1p, is an ER-localized protein that links the unfolded protein response and programmed cell death in Saccharomyces cerevisiae.
Yeast Bax inhibitor, Bxi1p, is an ER-localized protein that links the unfolded protein response and programmed cell death in Saccharomyces cerevisiae.
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DOI：
10.1371/journal.pone.0020882
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Austriaco N
中科院分区：
文献类型：
--
作者：
Cebulski J;Malouin J;Pinches N;Cascio V;Austriaco N
Bax抑制剂-1（BI-1）是一种抗凋亡基因，其表达在多种人类癌症中上调。在哺乳动物和植物细胞中的研究表明，BI-1蛋白存在于内质网中，并参与由ER应激触发的未折叠蛋白反应（UPR）。它被认为是通过涉及改变钙动力学的机制起作用的。在本文中，我们提供的证据表明，由开放阅读框，YNL 305 C，是一个真正的同源物BI-1的酿酒酵母蛋白编码。首先，我们证实了来自两种不同菌株背景的酵母细胞缺乏YNL 305 C，我们已将其重命名为BXI 1，它们对热休克诱导的细胞死亡比野生型对照更敏感，即使它们在30°C下的生长速率无法区分。它们也更容易受到乙醇诱导和葡萄糖诱导的程序性细胞死亡的影响。值得注意的是，我们发现Bxi 1 p-GFP与ER定位蛋白Sec 63 p-RFP共定位。我们还发现，Δ bxi 1细胞不仅对诱导ER应激的药物更敏感，而且用UPRE-lacZ报告基因测量的未折叠蛋白反应也减少。最后，我们发现，删除BXI 1减少了钙信号传导响应的积累，未折叠的蛋白质在ER中测量的钙调神经磷酸酶依赖性CDRE-lacZ报告。总的来说，我们的数据表明，Bxi 1 p，像它的后生动物同系物，是一个ER定位的蛋白质，连接未折叠的蛋白质反应和程序性细胞死亡。
Bax inhibitor-1 (BI-1) is an anti-apoptotic gene whose expression is upregulated in a wide range of human cancers. Studies in both mammalian and plant cells suggest that the BI-1 protein resides in the endoplasmic reticulum and is involved in the unfolded protein response (UPR) that is triggered by ER stress. It is thought to act via a mechanism involving altered calcium dynamics. In this paper, we provide evidence that the Saccharomyces cerevisiae protein encoded by the open reading frame, YNL305C, is a bona fide homolog for BI-1. First, we confirm that yeast cells from two different strain backgrounds lacking YNL305C, which we have renamed BXI1, are more sensitive to heat-shock induced cell death than wildtype controls even though they have indistinguishable growth rates at 30°C. They are also more susceptible both to ethanol-induced and to glucose-induced programmed cell death. Significantly, we show that Bxi1p-GFP colocalizes with the ER localized protein Sec63p-RFP. We have also discovered that Δbxi1 cells are not only more sensitive to drugs that induce ER stress, but also have a decreased unfolded protein response as measured with a UPRE-lacZ reporter. Finally, we have discovered that deleting BXI1 diminishes the calcium signaling response in response to the accumulation of unfolded proteins in the ER as measured by a calcineurin-dependent CDRE-lacZ reporter. In toto, our data suggests that the Bxi1p, like its metazoan homologs, is an ER-localized protein that links the unfolded protein response and programmed cell death.
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影响因子：
16
作者：
Chae, HJ;Kim, HR;Reed, JC
通讯作者：
Reed, JC
影响因子：
7.8
作者：
Ellis, Charissa D;Wang, Fudi;MacDiarmid, Colin W;Clark, Suzanne;Lyons, Thomas;Eide, David J
通讯作者：
Eide, David J
影响因子：
3.5
作者：
Chae, HJ;Ke, N;Reed, JC
通讯作者：
Reed, JC
DOI：
10.1073/pnas.211423998
发表时间：
2001-10-09
影响因子：
11.1
作者：
Kawai-Yamada, M;Jin, LH;Uchimiya, H
通讯作者：
Uchimiya, H
影响因子：
3.3
作者：
Bonilla, M;Cunningham, KW
通讯作者：
Cunningham, KW