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Wu GS, Burns TF, McDonald ER, Meng RD, Kao G, Muschel R, Yen T, El-Deiry WS
Induction of the TRAIL receptor KILLER/DR5 in p53-dependent apoptosis but not growth arrest
Oncogene (1999) 18:6411-6418.
Abstract
The TRAIL death receptor KILLER/DR5 is induced by DNA damaging agents in wild-type p53-expressing cells. Here me show that, unlike the p53-target CDK-inhibitor p21(WAF1/CIP1), the TRAIL death receptor KILLER/DR5 is only induced in cells undergoing p53-dependent apoptosis and not cell cycle arrest. Thus GM glioblastoma cells carrying an inducible MMTV-driven p53 gene undergo cell cycle arrest and upregulate p21 but not KILLER/DR5 expression upon dexamethasone exposure. W138 normal lung fibroblasts undergoing cell cycle arrest in response to ionizing irradiation also induce p21 but not KILLER/DR5 gene expression. KILLER/DR5 upregulation is also deficient in irradiated lymphoblastoid cells derived from patients with Ataxia Teleangiectasia suggesting a role for the ATM-p53 pathway in regulating KILLER/DR5 expression after DNA damage. Inhibition of transcription by Actinomycin D blocks both KILLER/DR5 and p21 induction in cells undergoing p53-dependent apoptosis. Our results suggest that the p53-dependent transcriptional induction of KILLER/DR5 death receptor is restricted to cells undergoing apoptosis and not cells undergoing exclusively p53-dependent GI arrest.
Note
Publication Date: 1999-11-11.
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Last updated on Wednesday, March 04, 2020