Fig. 3
From: Cell Cycle Exit: Growth Arrest, Apoptosis, and Tumor Suppression Revisited
(A) Genomic structure of the p16-p19ARF locus. Blue boxes denote open reading frame 1 (ORF 1) constituting the p16 transcript, red boxes indicate ORF 2 comprising the p19ARF mRNA, and yellow boxes represent p15 exons. The presumptive promoters for the three transcripts are marked by arrows. For simplicity, the locus is not drawn to scale; genomic analysis of the human locus containing p16 and p19ARF indicates that it is approximately 30 kb and that exons 1β and 1α are separated by ∼20 kb. (B) Schematic representation of p16 and postulated p19ARF pathways. The p16 pathway is simplified in this diagram. However, alterations in p16, CDK4, cyclin D, and pRB appear to be mutually exclusive within an individual cell, suggesting that they have functionally equivalent consequences. The inability of p19ARF to induce cell cycle arrest in cells lacking p53 suggests a functional pathway, although the inactivation of p53 in some tumors derived from p19ARF-null mice indicates that inactivation of these two genes is not functionally equivalent. The locus containing p16 and p19ARF has also been called the INK4a-ARF locus. [Adapted with permission from Haber, 199738.]