Molecular cloning and characterization of LZIC, a novel gene encoding ICAT homologous protein with leucine zipper domain.
ICAT inhibits the interaction between beta-catenin and TCF transcription factors. As ICAT might be a tumor suppressor gene with the potential to negatively regulate the WNT - beta-catenin - TCF signaling pathway, ICAT related gene in the human genome draft sequence was searched for. Here, the LZIC gene, a novel gene encoding a 190-amino-acid polypeptide with leucine zipper domain and ICAT homologous domain, was cloned and characterized. Amino-acid identity between LZIC and ICAT in the ICAT homologous domain was 38%. The LZIC gene, consisting of at least 8 exons, was located in the human chromosome 1p36.32-pter region. The major 5.2-kb LZIC mRNA and minor 2.1-, 1.6-, and 1.0-kb LZIC mRNAs were expressed almost ubiquitously in normal human tissues. LZIC was expressed in all cancer cell lines examined in this study, and was significantly up-regulated in a gastric cancer cell line MKN74 and 5 cases of primary gastric cancer. As LZIC contains ICAT homologous domain, LZIC might inhibit the interaction between beta-catenin and TCF transcription factors, just like ICAT, and, up-regulation of LZIC in gastric cancer might be due to a negative feed-back mechanism to inhibit the WNT - beta-catenin - TCF signaling pathway.
Katoh
M
M
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan. mkatoh@ncc.go.jp
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D020014:K562 Cells; D016350:Leucine Zippers / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C447999:LZIC protein, human; D012333:RNA, Messenger