Apoptosis-inhibiting activities of BIR family proteins in Xenopus egg extracts.
In many animal species including Xenopus, ovulated eggs possess an intrinsic apoptotic execution system. This program is inhibited for a limited time by some maternal apoptosis inhibitors, although their molecular properties remain uncharacterized. Baculovirus IAP repeat (BIR) family proteins contain evolutionarily conserved BIR domains and play important roles in apoptosis suppression, and are therefore good candidates as maternal apoptosis inhibitors. We identified four maternal BIR family proteins in Xenopus eggs and, using the biochemical advantages of egg extracts, examined their physiological functions. These molecules included two survivin-related proteins, xEIAP/XLX, and a possible ortholog of XIAP named xXIAP. The addition of recombinant xXIAP greatly delayed apoptotic execution, whereas the immunodepletion of endogenous xXIAP significantly accelerated the onset of apoptosis. In contrast, xEIAP/XLX was a poor apoptosis inhibitor, and neither of the survivin orthologs showed anti-apoptotic activity in our assay. Both xEIAP/XLX and xXIAP were degraded by activated caspases, and also by a novel proteolytic system that required the presence of C-terminal RING finger domain but was insensitive to proteasome inhibition. Our data suggest that the regulation of endogenous xXIAP concentration is important for the survival of Xenopus eggs.
Tsuchiya
Yuichi
Y
Department of Biochemistry, Toho University School of Medicine, Tokyo, Japan.
Murai
Shin
S
Yamashita
Shigeru
S
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009865:Oocytes / Q000502:physiology*; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*
C107489:BIRC5 protein, human; C519842:EIAP protein, Xenopus; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011506:Proteins; D011994:Recombinant Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D029867:Xenopus Proteins; D020928:Mitogen-Activated Protein Kinases