Evolution of p53 in hypoxia-stressed Spalax mimics human tumor mutation.

ABSTRACT: The tumor suppressor gene p53 controls cellular response to a variety of stress conditions, including DNA damage and hypoxia, leading to growth arrest and/or apoptosis. Inactivation of p53, found in 40-50% of human cancers, confers selective advantage under hypoxic microenvironment during tumor progression. The mole rat, Spalax, spends its entire life cycle underground at decidedly lower oxygen tensions than any other mammal studied. Because a wide range of respiratory adaptations to hypoxic stress evolved in Spalax, we speculated that it might also have developed hypoxia adaptation mechanisms analogous to the genetic/epigenetic alterations acquired during tumor progression. Comparing Spalax with human and mouse p53 revealed an arginine (R) to lysine (K) substitution in Spalax (Arg-174 in

SUBMITTER: Ashur-Fabian O 

PROVIDER: S-EPMC514462 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature