NR ANFJ
AU Paitel,E.; Fahraeus,R.; Checler,F.
TI Cellular prion protein sensitizes neurons to apoptotic stimuli through Mdm2-regulated and p53-dependent caspase 3-like activation
QU The Journal of Biological Chemistry 2003 Mar 21; 278(12): 10061-6
PT journal article
AB We examined the influence of cellular prion protein (PrPc) in the control of cell death in stably transfected TSM1 cells. PrPc expression enhanced staurosporine-stimulated neuronal toxicity and DNA fragmentation, caspase 3-like activity and immunoreactivity, and p53 immunoreactivity and transcriptional activities. Caspase activation was reduced by the chemical inhibitor of p53, pifithrin-alpha, as well as by PrPc- or p53-antisense approaches but remained insensitive to the Fyn kinase inhibitor PP2 (4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine). We establish that PrPc controls p53 at a post-transcriptional level and is reversed by Mdm2 transfection and p38 MAPK inhibitor. We propose that endogenous cellular prion protein sensitizes neurons to apoptotic stimuli through a p53-dependent caspase 3-mediated activation controlled by Mdm2 and p38 MAPK.
MH Animal; *Apoptosis; Caspases/*metabolism; DNA Fragmentation; Enzyme Activation; Mice; Mitogen-Activated Protein Kinases/physiology; Neurons/cytology/*drug effects; Prions/*toxicity; Protein p53/analysis/*physiology; Proto-Oncogene Proteins/*physiology; Staurosporine/pharmacology; Support, Non-U.S. Gov't
AD Institut de Pharmacologie Moleculaire et Cellulaire of CNRS, UMR6097, Valbonne, France.
SP englisch
PO USA