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- Title
p53 upregulates cFLIP, inhibits transcription of NF-κB-regulated genes and induces caspase-8-independent cell death in DLD-1 cells.
- Authors
Bartke, Till; Siegmund, Daniela; Peters, Nathalie; Reichwein, Monica; Henkler, Frank; Scheurich, Peter; Wajant, Harald
- Abstract
One of the main functions of the tumor suppressor p53 is the induction of programmed cell death. Here we investigated in detail the molecular mechanisms that underlay p53 transactivation-dependent apoptosis in the human colon cancer cell line DLD-1. Although p53 upregulated the death receptors Fas, TRAIL-R1 and TRAIL-R2 in this cell line, p53-induced cell death occurred without detectable caspase-8 activation whereas, activation of caspase-9 and caspase-3 was readily observed. In addition to the upregulation of death receptors, p53 induced the pro-apoptotic Bcl-2 family members Bik and Bak and downregulated the anti-apoptotic Bcl-xL protein. Moreover, in RNase protection assay analyses as well as in reporter gene analyses we found a p53-dependent upregulation of the death receptor-inhibitory protein cFLIP. Together, these data argue for a p53-mediated activation of the mitochondrial pathway of apoptosis. In contrast to recently published data obtained in different cellular systems, there was no evidence for an essential role of NF-κB in p53-induced cell death. Moreover, induction of p53 interfered with TNF-induced NF-κB activation independently from apoptosis-induction. Oncogene (2001) 20, 571–580.
- Subjects
CELL death; APOPTOSIS; COLON cancer
- Publication
Oncogene, 2001, Vol 20, Issue 5, p571
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1204124