Identification of a novel splice variant of X-linked inhibitor of apoptosis-associated factor 1.
XAF1 (XIAP-associated factor 1) binds to XIAP and blocks its anti-apoptotic activity. It has been reported that XAF1 is mainly expressed in normal tissues but is missing or present at low levels in most cancer cell lines, which implies a tumor-suppressing function. In the present study we describe the identification of a novel splice variant of human XAF1, designated XAF1C, which contains a cryptic exon. Incorporation of this exon (exon 4b) into the mRNA introduces an in-frame stop codon, resulting in a shortened open-reading frame (ORF) of 495 nucleotides. This ORF is predicted to encode a 164 amino acid (AA) protein lacking the C-terminal domain of the previously described XAF1(A), but containing a unique 24 AA carboxy terminus. Like XAF1(A), XAF1C mRNA expression was detected in a variety of human cancer cell lines and also in normal human tissues. The ratio of XAF1(A) and XAF1C mRNA expression differs amongst the cell lines tested, suggesting differential mRNA stabilities and/or the existence of tissue- or cell type-specific splicing regulation. In transfected cells, xaf1c encodes a truncated protein of 18kDa, which is distributed primarily in the nucleus.
Yin
Weihong
W
Department of Biochemistry and Molecular Biology, Louisiana State University Health Science Center School of Medicine in Shreveport and Feist-Weiller Cancer Center, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA 71130, USA.
Cheepala
Satish
S
Clifford
John L
JL
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004274:DNA, Recombinant / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity; D014018:Tissue Distribution; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D004274:DNA, Recombinant; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C417551:XAF1 protein, human; C496866:XIAP protein, human