The inhibitor-of-apoptosis protein Bir1p protects against apoptosis in S. cerevisiae and is a substrate for the yeast homologue of Omi/HtrA2

David Walter,Birthe Fahrenkrog,Silke Wissing,Frank Madeo

doi:10.1242/jcs.02902

Abstract

Inhibitor-of-apoptosis proteins (IAPs) play a crucial role in the regulation of metazoan apoptosis. IAPs are typically characterized by the presence of one to three baculovirus IAP repeat (BIR) domains that are essential for their anti-apoptotic activity. Bir1p is the sole BIR-protein in yeast and has been shown to participate in chromosome segregation events. Here, we show that Bir1p is a substrate for Nma111p, which is the homologue of the human pro-apoptotic serine protease Omi/HtrA2 and which is known to mediate apoptosis in yeast. Bir1p is a cytoplasmic and nuclear protein, and yeast cells lacking bir1 are more sensitive to apoptosis induced by oxidative stress. Consistently, overexpression of Bir1p reduces apoptosis-like cell death, whereas this protective effect can be antagonized in vivo by simultaneous overexpression of Nma111p. Moreover, chronologically aged cells that constitutively overexpress Bir1p show a delayed onset of cell death. Therefore, Bir1p, like its closest metazoan homologues deterin and survivin, has dual functions: it participates in chromosome segregation events and cytokinesis and exhibits anti-apoptotic activity.

Highlights

Apoptosis is a physiological form of programmed cell death vital to the development and maintenance of multicellular organisms
Inhibitor-of-apoptosis proteins (IAPs) are typically characterized by the presence of one to three baculovirus IAP repeat (BIR) domains that are essential for their anti-apoptotic activity
We show that Bir1p is a substrate for Nma111p, which is the homologue of the human pro-apoptotic serine protease Omi/HtrA2 and which is known to mediate apoptosis in yeast

Summary

Introduction

Apoptosis is a physiological form of programmed cell death vital to the development and maintenance of multicellular organisms. Not all BIRdomain-containing proteins (BIRPs) appear to have antiapoptotic properties, namely BIR-proteins in yeast, C. elegans, plants and protozoans (reviewed in Liston et al, 2003; Vaux and Silke, 2005; Verhagen et al, 2001). These BIRPs lack a RING domain and their BIR-domains are structurally different from the BIR-domains of IAPs. These BIRPs lack a RING domain and their BIR-domains are structurally different from the BIR-domains of IAPs They are referred as to type-II BIR domains, whereas IAPs harbour type-I BIRdomains. The Drosophila proteins Deterin and Bruce ( known as Apollon in mammals) and the murine protein TIAP, all type-II BIRPs, are able to inhibit apoptosis (Bartke et al, 2004; Hao et al, 2004; Jones et al, 2000; Vernooy et al, 2002)

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Discussion

Conclusion