Cell Division Regulation by BIR1, a Member of the Inhibitor of Apoptosis Family in Yeast

Abstract

The inhibitor of apoptosis (IAP) gene family comprises molecules that block the activity of pro-apoptotic caspase proteases. Paradoxically, yeasts contain IAP proteins but no caspases and no apoptotic program. To determine the function of these proteins<i>in vivo</i>, we disrupted the <i>BIR1</i> gene, encoding the only known IAP in yeast <i>Saccharomyces cerevisiae</i>. Sporulation of heterozygous diploids yielded no viable mutant haploids, indicating that <i>BIR1</i> is an essential gene. By flow cytometry, some heterozygous mutants were polyploid accumulating >4n DNA content. These cells exhibited a 20–40% reduction in growth rate, which was rescued by plasmid-borne over-expression of<i>BIR1</i> but not by its human counterpart, survivin. Deletion analysis revealed that the N-terminal domain of Bir1, containing the conserved baculovirus IAP repeat, was able to partially complement the cell growth defect caused by <i>BIR1</i> deletion. Moreover, the full-length and truncated forms of Bir1 accelerated cell division in wild-type cells. Finally, <i>BIR1</i> heterozygous mutants exhibited grossly altered cell morphology with mis-shapen or abnormally long buds connected to an unusually large mother cell. These findings identify a novel function of IAP proteins in the pleiotropic control of cell division, in addition to their role in the suppression of apoptosis.