Association of p14 super(ARF) with the p120 super(E4F) Transcriptional Repressor Enhances Cell Cycle Inhibition

The p14 super(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 super(ARF) forms a complex with the E1A-regulated transcriptional repressor, p120 super(E4F). p120 super(E4F) contacts p14 super(ARF) and p53 to form a ternary complex in vivo and enhances p14 super(ARF)-induced G sub(2) cell cycle arrest in a p53-dependent manner. We suggest that the interaction of p14 super(ARF) and p120 super(E4F) forms an important link between the p14 super(ARF) and p53 tumor suppressor proteins, both of which exhibit enhanced cell cycle inhibitory activity in the presence of this transcriptional repressor.