p53 is involved in the p120E4F-mediated growth arrest

Control of cell growth and division by the p53 tumor suppressor protein req uires its abilities to transactivate and repress specific target genes and to associate in complex with other proteins. Here we demonstrate that p53 b inds to the E1A-regulated transcription factor p120E4F, a transcriptional r epressor of the adenovirus E4 promoter. The interaction involves carboxy-te rminal half of p120E4F and sequences located at the end of the sequence-spe cific DNA-binding domain of p53, Ectopic expression of p120E4F leads to a b lock of cell proliferation in several human and murine cell lines and this effect requires the association with wild-type (wt) p53, Although p120E4F c an also bind to mutant p53, the growth suppression induced by overexpressio n of the protein is severely reduced in a cell line that contains mutant p5 3. These data suggest that p120E4F may represent an important element withi n the complex network of p53 checkpoint functions.