Splice variants of mIAP1 have an enhanced ability to inhibit apoptosis.
c-IAP1 is a member of the Inhibitor of Apoptosis protein family. Functions ascribed to c-IAP1 include inhibition of apoptosis and activation of NF-kappaB. Herein, we show that murine c-IAP1 (mIAP1) undergoes alterative splicing, generating two truncated proteins; one that lacks the CARD and RING domains (mIAP1-DeltaCARDDeltaRING) and the other that lacks only the CARD domain (mIAP1-DeltaCARD). mIAP1-DeltaCARDDeltaRING mRNA is expressed at 2-3% of the levels of full-length mIAP1 (FL-mIAP1) in mouse tissues, yet it encodes a protein that accumulates at 50-fold higher levels than the FL-mIAP1 in cultured cells. This protein has an enhanced ability to inhibit Bax-induced apoptosis, but does not activate an NF-kappaB reporter. In contrast to mIAP1-DeltaCARDDeltaRING, the mIAP1-DeltaCARD mRNA displays distinct tissue variation, ranging from 5% to 15% of the FL-mIAP1 mRNA levels and its levels increase in the mammary gland during involution. This isoform also has enhanced anti-apoptotic activity, but diminished NF-kappaB activation. In summary, mIAP1 is alternatively spliced, generating protein isoforms with distinct functional characteristics.
Mosley
Jonathan D
JD
Department of Pharmacology, Case School of Medicine, Cleveland, OH 44106, USA.
Keri
Ruth A
RA
D017398:Alternative Splicing / Q000235:genetics* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000502:physiology; D007438:Introns / Q000235:genetics; D008297:Male; D051379:Mice; D022821:RNA Splice Sites / Q000235:genetics; D014162:Transfection; D044767:Ubiquitin-Protein Ligases
D051034:Inhibitor of Apoptosis Proteins; D022821:RNA Splice Sites; C494834:Birc2 protein, mouse; D044767:Ubiquitin-Protein Ligases