TY - JOUR
T1 - p53 is necessary for the apoptotic response mediated by a transient increase of Ras activity
AU - Ma, Peihong
AU - Magut, Maureen
AU - Chen, Xinbin
AU - Chen, Chang Yan
PY - 2002
Y1 - 2002
N2 - The tumor suppressor p53 eliminates cancer-prone cells via multiple mechanisms, including apoptosis. Ras elicits apoptosis in cells after protein kinase C (PKC) downregulation. However, the role of p53 in Ras-mediated apoptosis has not been fully investigated. Here, we demonstrate that mouse fibroblasts that express wild-type p53 are more susceptible to apoptosis elicited by PKC inhibition if Ras is transiently expressed or upregulated as opposed to stably expressed. In the latter case, p53 is frequently mutated. Transiently increased Ras activity induces Bax, and PKC inhibition augments this induction. Overexpression of E6 inactivates p53 and thereby suppresses both Bax induction and apoptosis. In contrast, Bax is not induced in stable ras transfectants, regardless of PKC inhibition. The data suggest that short- and long-term activation of Ras use a different mechanism(s) to initiate apoptosis. The status of p53 may contribute to such differences.
AB - The tumor suppressor p53 eliminates cancer-prone cells via multiple mechanisms, including apoptosis. Ras elicits apoptosis in cells after protein kinase C (PKC) downregulation. However, the role of p53 in Ras-mediated apoptosis has not been fully investigated. Here, we demonstrate that mouse fibroblasts that express wild-type p53 are more susceptible to apoptosis elicited by PKC inhibition if Ras is transiently expressed or upregulated as opposed to stably expressed. In the latter case, p53 is frequently mutated. Transiently increased Ras activity induces Bax, and PKC inhibition augments this induction. Overexpression of E6 inactivates p53 and thereby suppresses both Bax induction and apoptosis. In contrast, Bax is not induced in stable ras transfectants, regardless of PKC inhibition. The data suggest that short- and long-term activation of Ras use a different mechanism(s) to initiate apoptosis. The status of p53 may contribute to such differences.
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U2 - 10.1128/MCB.22.9.2928-2938.2002
DO - 10.1128/MCB.22.9.2928-2938.2002
M3 - Article
C2 - 11940651
AN - SCOPUS:0036240612
VL - 22
SP - 2928
EP - 2938
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 9
ER -