| First Author | Paitel E | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 12 | Pages | 10061-6 |
| PubMed ID | 12529324 | Mgi Jnum | J:82585 |
| Mgi Id | MGI:2653754 | Doi | 10.1074/jbc.M211580200 |
| Citation | Paitel E, et al. (2003) Cellular prion protein sensitizes neurons to apoptotic stimuli through Mdm2-regulated and p53-dependent caspase 3-like activation. J Biol Chem 278(12):10061-6 |
| abstractText | We examined the influence of cellular prion protein (PrP(c)) in the control of cell death in stably transfected TSM1 cells. PrP(c) 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 PrP(c)- 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 PrP(c) 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. |
