Induction of ARF tumor suppressor gene expression and cell cycle arrest bytranscription factor DMP1

Expression of the DMP1 transcription factor, a cyclin D-binding Myb-like pr otein, induces growth arrest in mouse embryo fibroblast strains but is devo id of antiproliferative activity in primary diploid fibroblasts that lack t he ARF tumor suppressor gene. DMP1 binds to a single canonical recognition site in the ARF promoter to activate gene expression, and in turn, p19(ARF) synthesis causes p53-dependent cell cycle arrest. Unlike genes such as Myc , adenovirus E1A, and E2F-1, which, when overexpressed, activate the ARF-p5 3 pathway and trigger apoptosis, DMP1, like ARF itself, does not induce pro grammed cell death. Therefore, apart from its recently recognized role in p rotecting cells from potentially oncogenic signals, ARF can be induced in r esponse to antiproliferative stimuli that do not obligatorily lead to apopt osis.