The mammalian INK4a/ARF locus encodes two linked tumor suppressor proteins, p16INK4a
and ARF, which respectively regulate the retinoblastoma (RB) and p53 pathways. Genetic
data have firmly established that both proteins possess significant in vivo tumor suppressor
activity. In addition to their non-overlapping roles in preventing cancer, one or both proteins
are induced under certain circumstances in most cultured murine and human cell types, and
thereby are critical effectors of senescence. Likewise, data from murine models have …