title: The Regulation of Cellular Functions by the p53 Protein: Cellular Senescence.
abstract: Transformed cells have properties that allow them to survive and proliferate inappropriately. These characteristics often arise as a result of mutations caused by DNA damage. p53 suppresses transformation by removing the proliferative or survival capacity of cells with DNA damage or inappropriate cell-cycle progression. Cellular senescence, marked by morphological and gene expression changes, is a critical component of p53-mediated tumor suppression. In response to stress, p53 can facilitate an arrest and senescence program in cells exposed to stresses such as DNA damage and oncogene activation, preventing transformation. Senescent cells are evident in precancerous adenoma-type lesions, whereas proliferating, malignant tumors have bypassed senescence, either by p53 mutation or inactivation of the p53 pathway by other means. Tumors that have retained wild-type p53 often show a p53-mediated senescence response to chemotherapy. This response is actually detrimental in some tumor types, as senescent cells can drive relapse by persisting and producing cytokines and chemokines through an acquired secretory phenotype.
authors.affiliation: Department of Biochemistry and Molecular Biology, Tulane School of Medicine, New Orleans, Louisiana 70112.
authors.forename: Crystal A
authors.initials: CA
authors.lastname: Tonnessen-Murray
authors.affiliation: Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030.
authors.forename: Guillermina
authors.initials: G
authors.lastname: Lozano
authors.affiliation: Department of Biochemistry and Molecular Biology, Tulane School of Medicine, New Orleans, Louisiana 70112.
authors.forename: James G
authors.initials: JG
authors.lastname: Jackson
mesh_terms: D002455:Cell Division / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics*; D004249:DNA Damage; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology
chemical_list: D016159:Tumor Suppressor Protein p53