Search

Aneuploidy is the genetic state of a cell that has a chromosomal number that is not an exact multiple of the haploid complement. It is a leading cause of spontaneous abortions and of mental retarda...

Bax inhibitor-1 (BXI1) is an anti apoptotic gene whose human homolog's expression is upregulated in a wide range of human cancers. Studies have shown that Bxi1p is localized in the endoplasmic reticulum and is involved in the unfolded protein response (UPR) that is triggered by endoplasmic reticulum (ER) stress. BXI1 is thought to act via a mechanism involving altered calcium dynamics. In this poster, we provide evidence that suggests that the Saccharomyces cerevisiae protein facilitates Ire1p clustering in response to ER stress and alters calcium signaling. With DTT induction experiments using Δbxi1 mutants and different UPR GFP reporters, we have confirmed our published data that suggests that BXI1 is involved in the UPR, Intriguingly, our preliminary data suggests that Bxi1p facilitates clustering of Ire1p during ER stress. [Our laboratory is supported by grant NIGMS R15 GM110578, awarded to N. Austriaco.]

Deletion of the Saccharomyces gene, UTH1, a founding member of the SUN family of fungal genes, has pleiotropic effects. Several phenotypes of Deltauth1 cells including their decreased levels of mitochondrial proteins, their impaired autophagic degradation of mitochondria, and their increased viability in the presence of mammalian BAX, a proapoptotic regulator localized to the mitochondria, have prompted others to propose that the Uth1p functions primarily at the mitochondria. In this report, we show that cells lacking UTH1 have more robust cell walls with higher levels of beta-d-glucan that allows them to grow in the presence of calcofluor white or sodium dodecyl sulfate, two reagents known to perturb the yeast cell wall. Moreover, these Deltauth1 cells are also significantly more resistant to spheroplast formation induced by zymolyase treatment than their wild-type counterparts. Surprisingly, our data suggest that several of the enhanced growth phenotypes of Deltauth1 cells, including their resistance to BAX-mediated toxicity, arise from a strengthened cell wall. Therefore, we propose that Uth1p's role at the cell wall and not at the mitochondria may better explain many of its effects on yeast physiology and programmed cell death.