Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distribution pattern.
Using homology searches, we identified a novel human inhibitor of apoptosis (IAP) gene. This gene has two splicing variants that contain open reading frames of 298 and 280 amino acids and both contained a single copy of baculovirus IAP repeat (BIR) and RING domain. We refer here to the longer and shorter variants as Livin alpha and beta, respectively. Semiquantitative reverse transcriptase-polymerase chain reaction demonstrated a tissue-specific and non-correlated expression pattern in both adult and fetal tissues. Both mRNA variants were detected in various transformed cell lines. Despite their very close similarity, the two isoforms have different antiapoptotic properties. Both isoforms have a significant antiapoptotic activity in the Jurkat T cell line after triggering apoptosis via tumor necrosis factor and CD95 receptors. The Livin alpha but not beta protects cells from apoptosis induced by staurosporine, but in contrast, apoptosis initiated by etoposide was blocked only by the beta isoform. This difference in biological activities may indicate the presence of critical amino acids outside the BIR and RING domains. These functional and tissue distribution differences of Livin alpha and beta suggest that Livin may play a complex role in the regulation of apoptosis.
Ashhab
Y
Y
Department of Hematology, Hadassah University Hospital, Ein-Karem, P.O. Box 12000, Jerusalem 91120, Israel.
Alian
A
A
Polliack
A
A
Panet
A
A
Ben Yehuda
D
D
D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing / Q000235:genetics*; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D002461:Cell Line, Transformed; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019169:Jurkat Cells / Q000166:cytology / Q000187:drug effects; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009928:Organ Specificity; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D019311:Staurosporine / Q000494:pharmacology; D000077022:Survivin; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; C107489:BIRC5 protein, human; C419866:BIRC7 protein, human; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011506:Proteins; D000077022:Survivin; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D005047:Etoposide; D019311:Staurosporine