The Arf/p53 pathway in cancer and aging.
Arf and p53 are regarded among the most relevant tumor suppressors based on their ubiquitous and frequent inactivation in human cancer. The Arf/p53 pathway protects cells against several types of damage and this is the basis of its tumor suppressor activity. Interestingly, aging is a process associated with the accumulation of damage derived from chronic stresses of small magnitude. In agreement with its damage protection role, it has been recently described that the Arf/p53 pathway not only protects mammalian organisms from cancer but also from aging. However, there is also evidence that p53, under certain circumstances, such as when constitutively active, can induce aging. We discuss here the current evidence linking the Arf/p53 pathway to the process of aging and present a unified model.
Matheu
Ander
A
Tumor Suppression Group, Spanish National Cancer Research Center, Madrid, Spain.
Maraver
Antonio
A
Serrano
Manuel
M
D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53