Identification of a gene that reverses the immortal phenotype of a subset of cells and is a member of a novel family of transcription factor-like genes

Based on the dominance of cellular senescence over immortality, immortal hu man cell lines have been assigned to four complementation groups for indefi nite division. Human chromosomes carrying senescence genes have been identi fied, including chromosome 4. We report the cloning and identification of a gene, mortality factor 4 (MORF 4), which induces a senescent-like phenotyp e in immortal cell lines assigned to complementation group B with concomita nt changes in two markers for senescence. MORF 4 is a member of a novel fam ily of genes with transcription factor-like motifs, We present here the seq uences of the seven family members, their chromosomal locations, and a part ial characterization of the three members that are expressed. Elucidation o f the mechanism of action of these genes should enhance our understanding o f growth regulation and cellular aging.