Molecular cloning and characterization of ST7R (ST7-like, ST7L) on human chromosome 1p13, a novel gene homologous to tumor suppressor gene ST7 on human chromosome 7q31

Abstract

ST7 is a tumor suppressor gene, which is clustered with WNT2 gene in human chromosome 7q31 region. WNT2 gene is homologous to WNT2B gene. WNT2B gene encodes two isoforms due to alternative splicing of alternative promoter type. WNT2 and WNT2B isoform 2 (WNT2B2) are positive regulators of the WNT - beta-catenin - TCF signaling pathway. Here, a novel ST7-related gene ST7R (ST7-like, ST7L) was identified by using bioinformatics, and ST7R cDNAs were isolated by using cDNA-PCR. ST7R gene encoded 575-amino-acid polypeptide with leucine zipper domain and 3 tyrosine-phosphorylation sites. Human ST7R was homologous to human ST7 (72.1% total-amino-acid identity) and Drosophila CG3634 (56.8% total-amino-acid identity). Leucine zipper domain was unique to ST7R. Tyr 268 and Tyr 441 of ST7R were conserved in ST7 and CG3634. ST7R-homologous domains (S7H1, S7H2, and S7H3) were conserved among ST7R, ST7, and CG3634. ST7R gene consisted of at least 15 exons, and four ST7R isoforms were transcribed due to alternative splicing. ST7R and WNT2B genes, located in human chromosome 1p13 region, were clustered in tail-to-tail manner with an interval of less than 5.0-kb. ST7R-WNT2B and ST7-WNT2 gene clusters might be generated due to duplication of an ancestral gene cluster. Because allelic loss or rearrangements of human chromosome 1p13 region are reported in breast cancer, germ cell tumors, squamous cell carcinoma of head and neck, non-small cell lung cancer, gastrointestinal stromal/smooth muscle tumors (GIST), meningioma, melanoma, acute megakaryoblastic leukemia (M7), and Kaposi's sarcoma, ST7R might be a novel tumor suppressor gene on human chromosome 1p13.