The human 1-8D gene (IFITM2) is a novel p53 independent pro-apoptotic gene

Abstract

The human 1-8 interferon inducible gene family consists of at least 3 functional genes; 9-27, 1-8D and 1-8U, which are all linked on an 18-kb fragment of chromosome 11 and are highly homologous. It has recently been shown by us and others that the 1-8D gene is overexpressed in colon carcinoma. Here, we show, by sequence comparison of the 1-8D in pairs of tumor/normal colon tissues, the existence of 6 different alleles, containing single-nucleotide polymorphisms with no mutations. Transformation assays revealed a possible role for the 1-8D gene as a transformation inhibitor. Further, transient expression of the human 1-8D gene in multiple mammalian cell lines showed accumulation of cells in the G1 phase followed by elevation in the subG1 phase. SubG1 elevation was confirmed as apoptosis by Annexin-V binding assays and transferase-mediated dUTP nick end labeling assays. Moreover, knock-down of 1-8D provided partial protection from Etoposide and UV-induced apoptosis. The induction of apoptosis by 1-8D is dependent on caspase activities but not on p53 expression. Although 1-8D induces apoptosis independently of p53, p53 expression downregulates 1-8D protein expression. Our data suggest a role for the 1-8D gene as a novel pro-apoptotic gene that will provide new insights into the regulated cellular pathways to death.