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Yeast Bax Inhibitor, Bxi1p, Is An ER‐localized Protein that Regulates Calcium Levels and the Unfolded Protein Response
Author(s) -
Cebulski James,
Malouin Joshua,
Pinches Nathan,
Cascio Vincent,
Austriaco Nicanor
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.943.3
Subject(s) - unfolded protein response , endoplasmic reticulum , cytoplasm , saccharomyces cerevisiae , yeast , microbiology and biotechnology , calcineurin , biology , cell , apoptosis , reporter gene , chemistry , gene , biochemistry , gene expression , medicine , transplantation
Bax Inhibitor‐1 (BI‐1) was first identified by its ability to block Bax‐induced programmed cell death in the budding yeast, Saccharomyces cerevisiae. Significantly, overexpression of BI‐1 has been associated with several kinds of cancers in human patients including pulmonary adenocarcinoma. Recent studies in mammalian and plant cells have suggested that BI‐1 is involved in the cell's response to endoplasmic reticulum stress. To better understand the function of BI‐1, we are characterizing the yeast homolog of BI‐1, which we are calling BXI1. We have shown that Bxi1p‐GFP colocalizes with the ER localized protein Sec63p‐RFP. We have also discovered that cells lacking BXI1 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. This suggests that Bxi1p is involved in the yeast cells response to ER stress. We have also discovered that Δbxi1cells have a decreased response to changes in cytoplasmic calcium as measured by a calcineurin‐dependent CDRE‐lacZ reporter. In toto, our data suggests that the BXI1 gene may be involved in an ER‐associated pathway that is linked to the regulation of Ca2+ levels within the yeast cell. [Supported by NIGMS R15 GM094712, NSF MRI‐R2 0959354, and NIH Grant 2 P20 RR016457 to the Rhode Island INBRE Program.]