TheS. cerevisiaeHtrA-like protein Nma111p is a nuclear serine protease that mediates yeast apoptosis

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Abstract
The yeast S. cerevisiae can undergo programmed cell death that exhibits the typical cellular markers of apoptosis. The mammalian HtrA2 protein was recently reported to mediate apoptosis in a serine-protease-dependent manner owing to its ability to antagonise the inhibitor of apoptosis protein XIAP. Here, we report the identification and characterisation of the S. cerevisiae HtrA-like protein, which we termed Nma111p (for nuclear mediator of apoptosis), as a mediator of yeast apoptosis. Nma111p is a nuclear protein that, under cellular stress conditions (i.e. at elevated temperature or after induction of apoptosis by H2O2), tends to aggregate inside the nucleus without its expression level being upregulated, suggesting that aggregation of Nma111p is correlated to its death-mediating character. Nma111p belongs to the HtrA family of serine proteases and its pro-apoptotic activity depends on its serine-protease activity. Yeast cells that lack Nma111p survive better at 50°C than wild-type cells and the cells show no apoptotic hallmarks, such as chromatin condensation and fragmentation, or accumulation of reactive oxygen species, after the induction of apoptosis by H2O2. By contrast, overexpression of Nma111p enhances apoptotic-like cell death. Therefore, Nma111p, like its mammalian homologue HtrA2, mediates apoptosis.