TY - JOUR
T1 - The regulation of cellular functions by the p53 protein
T2 - Cellular senescence
AU - Tonnessen-Murray, Crystal A.
AU - Lozano, Guillermina
AU - Jackson, James G.
N1 - Publisher Copyright:
© 2017 Cold Spring Harbor Laboratory Press. All rights reserved.
PY - 2017/2
Y1 - 2017/2
N2 - 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 programin 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.
AB - 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 programin 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.
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U2 - 10.1101/cshperspect.a026112
DO - 10.1101/cshperspect.a026112
M3 - Article
C2 - 27881444
AN - SCOPUS:85011593467
SN - 2157-1422
VL - 7
JO - Cold Spring Harbor Perspectives in Medicine
JF - Cold Spring Harbor Perspectives in Medicine
IS - 2
M1 - a026112
ER -