p300 activation by Presenilin 1 but not by its M146L mutant

• Published in: Neuroscience letters 2007-02, Vol.413 (2), p.137-140
• Main Authors: Francis, Yitshak I., Diss, James K.J., Kariti, Moshe, Stephanou, Anastasis, Latchman, David S.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer's disease; Animals; Biological and medical sciences; Cell Line, Transformed; Cell Survival - genetics; CREB-Binding Protein - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; E1A-Associated p300 Protein - genetics; E1A-Associated p300 Protein - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - genetics; Medical sciences; Mutation - genetics; Nerve Degeneration - genetics; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Neurology; Neurons - metabolism; p300; Presenilin 1; Presenilin-1 - genetics; Presenilin-1 - metabolism; Rats; Transcriptional Activation - genetics; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2006.11.036

The transcriptional co-activator p300 plays an important role in regulating gene expression in a number of different cell types. We have shown that wild type (WT) Presenilin 1 (PS1) stimulates the transcriptional activity ability of CREB Binding Protein (CBP), a close homolog of p300, whereas the Alzheimer's disease (AD) associated mutant of PS1 does not have this effect. A recent report has suggested that mutant PS1 can also disrupt the TCF/β-catenin/CBP interaction but has no effect on the TCF/β-catenin/p300 interaction. This suggests that the malregulation of CBP, but not of p300, caused by mutation in PS1 may be involved in the disease process. Here we show that wild type PS1 stimulates the transcriptional activity ability of p300 whereas an Alzheimer's disease-associated mutant of PS1 did not produce this effect. To our knowledge, this is the first report that shows regulation of p300 activity by WT PS1 and not by mutant PS1, indicating that like CBP, p300 can be differentially regulated by WT PS1 compared to its AD- associated mutant.