The inhibitor-of-apoptosis protein Bir1p protects against apoptosis in S. cerevisiae and is a substrate for the yeast homologue of Omi/HtrA2.
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.
Walter
David
D
M. E. Müller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Wissing
Silke
S
Madeo
Frank
F
Fahrenkrog
Birthe
B
D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C511243:NMA111 protein, S cerevisiae; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2