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Yeast Bax Inhibitor, Bxi1p, Is an ER-Localized Protein That Links the Unfolded Protein Response and Programmed Cell Death in Saccharomyces cerevisiae (Paper)

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.

Bax inhibitor-1 (BI-1) was first cloned in mammals from adult testes of different species, as the testis enhanced gene transcript (TEGT). However, its anti-apoptotic function was identified several years later through a functional yeast screen designed to select for human cDNAs that inhibit BAX induced apoptosis. Importantly, BI-1 also suppressed apoptosis induced by BAX in human 293 kidney cells.

The anti-apoptotic function of BI-1 contributes to the development of cancer: BI-1 expression is upregulated in human breast cancer, prostate cancer, brain tumors, large cell lymphoma, and cervical cancer. In contrast, down-regulation of the gene is associated with the progression of chronic liver disease. More recent work has also revealed that overexpressing BI-1 not only transforms NIH3T3 cells but also enhances cancer metastasis by altering glucose metabolism and activating the sodium-hydrogen exchanger. Finally, two groups have shown that overexpression of the protein protects animals from obesity-associated insulin resistance and stroke and traumatic brain injury.

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