p19ARF links the tumour suppressor p53 to Ras

✍ Scribed by Palmero, Ignacio; Pantoja, Cristina; Serrano, Manuel

• Book ID: 109697728
• Publisher: Nature Publishing Group
• Year: 1998
• Tongue: English
• Weight: 185 KB
• Volume: 395
• Category: Article
• ISSN: 0028-0836
• DOI: 10.1038/25870

✦ Synopsis

p53 (refs 4, 8). This link between E2F-1 function and p14 ARF expression provides an explanation for the ability of oncogenic stimuli that could deregulate E2F-1 activity, such as defects in the RB pathway or activation of oncogenes such as Ras, E1A or Myc, to activate p53 (refs 9-12). Thus, abnormal proliferation, resulting in deregulated E2F-1 activity, would induce p14 ARF and stabilize p53 (Fig. ). This would lead to cell-cycle arrest or apoptosis unless a second lesion occurred, such as a mutation in p14 ARF or p53 itself.This model is supported by the observation that tumours containing p14 ARF mutations can tolerate the retention of wild-type p53 (refs 4, 8), strongly suggesting that loss of this pathway linking deregulated E2F-1 to the activation of p53 is an essential step in malignant progression.