Induction of the TRAIL receptor KILLER/DR5 in p53-dependent apoptosis but not growth arrest

The TRAIL death receptor KILLER/DR5 is induced by DNA damaging agents in wi ld-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 induc ed in cells undergoing p53-dependent apoptosis and not cell cycle arrest. T hus GM glioblastoma cells carrying an inducible MMTV-driven p53 gene underg o cell cycle arrest and upregulate p21 but not KILLER/DR5 expression upon d examethasone exposure. W138 normal lung fibroblasts undergoing cell cycle a rrest in response to ionizing irradiation also induce p21 but not KILLER/DR 5 gene expression. KILLER/DR5 upregulation is also deficient in irradiated lymphoblastoid cells derived from patients with Ataxia Teleangiectasia sugg esting a role for the ATM-p53 pathway in regulating KILLER/DR5 expression a fter DNA damage. Inhibition of transcription by Actinomycin D blocks both K ILLER/DR5 and p21 induction in cells undergoing p53-dependent apoptosis. Ou r results suggest that the p53-dependent transcriptional induction of KILLE R/DR5 death receptor is restricted to cells undergoing apoptosis and not ce lls undergoing exclusively p53-dependent GI arrest.