The INK4A/ARF locus:: Role in cell cycle control and apoptosis and implications for glioma growth

The unique INK4A/ARF locus at chromosome 9p21 encodes two distinct proteins that intimately link the pRB and p53 tumour suppressor pathways. p16(INK4A) has been identified as an inhibitor of the cell cycle, capable of inducing arrest in G1 phase. p14/p19(ARF) on the other hand can induce both G1 and G2 arrest due to its stabilizing effects on the p53 transcription factor. In addition to their roles in growth arrest, both proteins are involved in cellular senescence and apoptosis. The frequent mutation or deletion of INK4A/ARF in human tumours as well as the occurence of tumours in the murine knockout models have identified both p16 and ARF as bona fide tumour suppressors.