AbstractThe 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. © 2009 UICC