Association of p14^ARF with the p120^E4F transcriptional repressor enhances cell cycle inhibition

The p14^ARF tumor suppressor is a key regulator of cellular proliferation and is frequently inactivated in human cancer. This tumor suppressor functions in the p53 and pRb cell cycle regulatory pathways and can effectively activate both pathways to induce growth arrest or cell death. We now report that p14^ARF forms a complex with the E1A-regulated transcriptional repressor, p120^E4F. p120^E4F contacts p14^ARF and p53 to form a ternary complex in vivo and enhances p14^ARF-induced G₂ cell cycle arrest in a p53-dependent manner. We suggest that the interaction of p14^ARF and p120^E4F forms an important link between the p14^ARF and p53 tumor suppressor proteins, both of which exhibit enhanced cell cycle inhibitory activity in the presence of this transcriptional repressor.