| First Author | Vincent B | Year | 2009 |
| Journal | J Neurosci | Volume | 29 |
| Issue | 20 | Pages | 6752-60 |
| PubMed ID | 19458243 | Mgi Jnum | J:148840 |
| Mgi Id | MGI:3847007 | Doi | 10.1523/JNEUROSCI.0789-09.2009 |
| Citation | Vincent B, et al. (2009) p53-Dependent transcriptional control of cellular prion by presenilins. J Neurosci 29(20):6752-60 |
| abstractText | The presenilin-dependent gamma-secretase processing of the beta-amyloid precursor protein (betaAPP) conditions the length of the amyloid beta peptides (Abeta) that accumulate in the senile plaques of Alzheimer's disease-affected brains. This, together with an additional presenilin-mediated epsilon-secretase cleavage, generates intracellular betaAPP-derived fragments named amyloid intracellular domains (AICDs) that regulate the transcription of several genes. We establish that presenilins control the transcription of cellular prion protein (PrP(c)) by a gamma-secretase inhibitor-sensitive and AICD-mediated process. We demonstrate that AICD-dependent control of PrP(c) involves the tumor suppressor p53. Thus, p53-deficiency abolishes the AICD-mediated control of PrP(c) transcription. Furthermore, we show that p53 directly binds to the PrP(c) promoter and increases its transactivation. Overall, our study unravels a transcriptional regulation of PrP(c) by the oncogene p53 that is directly driven by presenilin-dependent formation of AICD. Furthermore, it adds support to previous reports linking secretase activities involved in betaAPP metabolism to the physiology of PrP(c). |
