The Yeast Homolog of the Mammalian Oncogene, Bax Inhibitor‐1, Regulates the Unfolded Protein Response by Altering the ER Microenvironment.

Abstract

Bax inhibitor‐1 (BI‐1) is an anti‐apoptotic gene whose expression is upregulated in a wide range of human cancers. The yeast homolog of BI‐1, yeast Bax inhibitor‐1 (BXI1), encodes a protein that belongs to the Bax Inhibitor (TMBIM) family of proteins. The crystal structure of a prokaryotic member of the family, BsYetJ, has revealed that the Bax inhibitor proteins are pH sensitive calcium leaks. Our studies have shown that yeast Bxi1p is localized to the ER and is involved in the unfolded protein response (UPR) that is triggered by ER stress. We have recently found that Bxi1p regulates the UPR downstream of endonuclease Ire1p clustering but upstream of HAC1 mRNA splicing. Studies with an ER localized calcium reporter and an ER redox reporter suggest that Bxi1p accomplishes this by altering the ER microenvironment.Support or Funding InformationOur laboratory is supported by grant NIGMS R15 GM110578, awarded to N. Austriaco.