p300 activation by Presenilin 1 but not by its M146L mutant.

Abstract

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/beta-catenin/CBP interaction but has no effect on the TCF/beta-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.

• Authors: Yitshak I Francis, James K J Diss, Moshe Kariti, Anastasis Stephanou, David S Latchman
• Journal: Neuroscience letters (Neurosci Lett) Vol. 413 Issue 2 Pg. 137-40 (Feb 14 2007) ISSN: 0304-3940 [Print] Ireland
• PMID: 17197080 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Presenilin-1
• CREB-Binding Protein
• Crebbp protein, rat
• E1A-Associated p300 Protein
• Ep300 protein, rat

Topics

• Alzheimer Disease (genetics, metabolism, physiopathology)
• Animals
• CREB-Binding Protein (metabolism)
• Cell Line, Transformed
• Cell Survival (genetics)
• E1A-Associated p300 Protein (genetics, metabolism)
• Gene Expression Regulation (genetics)
• Mutation (genetics)
• Nerve Degeneration (genetics, metabolism, physiopathology)
• Neurons (metabolism)
• Presenilin-1 (genetics, metabolism)
• Rats
• Transcriptional Activation (genetics)