A highly conserved proapoptotic gene, IKIP, located next to the APAF1 gene locus, is regulated by p53

• Published in: Cell death and differentiation Vol. 11; no. 12; pp. 1317 - 1325
• Main Authors: Hofer-Warbinek, R, Schmid, J A, Mayer, H, Winsauer, G, Orel, L, Mueller, B, Wiesner, Ch, Binder, B R, de Martin, R
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.12.2004
• Subjects: Alternative Splicing - genetics; Amino Acid Sequence - genetics; Animals; Apoptosis; Apoptosis - genetics; Apoptotic Protease-Activating Factor 1; Base Sequence - genetics; Biology; Carrier Proteins - genetics; Carrier Proteins - isolation & purification; Carrier Proteins - metabolism; Cattle; Cell Cycle Proteins - genetics; Cell Cycle Proteins - isolation & purification; Cell Cycle Proteins - metabolism; Cell death; Cell Line; Chromosomes, Human, Pair 12 - genetics; Conserved Sequence - genetics; Cytochrome; DNA, Complementary - analysis; DNA, Complementary - genetics; Endoplasmic reticulum; Exons - genetics; Gene Expression Regulation - genetics; Genes; Humans; I-kappa B Kinase; Kinases; Mice; Mitochondria; Molecular Sequence Data; Promoter Regions, Genetic; Protein Isoforms - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Proteins - genetics; Proteins - metabolism; Rats; Signal Transduction - genetics; Transcription factors; Transcription, Genetic - genetics; Transfection; Tumor necrosis factor-TNF; Tumor Suppressor Protein p53 - metabolism; Up-Regulation - genetics; Up-Regulation - radiation effects; X-Rays; Xenopus; Austria
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/sj.cdd.4401502

We describe here the identification and initial characterization of a novel human gene termed IKIP (I kappa B kinase interacting protein) that is located on chromosome 12 in close proximity to APAF1 (apoptotic protease-activating factor-1). IKIP and APAF1 share a common 488 bp promoter from which the two genes are transcribed in opposite directions. Three IKIP transcripts are generated by differential splicing and alternative exon usage that do not show significant homology to other genes in the databases. Similar to APAF1, expression of IKIP is enhanced by X-irradiation, and both genes are dependent on p53. Moreover, IKIP promotes apoptosis when transfected into endothelial cells. We conclude that IKIP is a novel p53 target gene with proapoptotic function.