The amyloid-beta peptide binds to cyclin B1 and increases human cyclin-dependent kinase-1 activity.

Abstract

The pathological features of Alzheimer's disease include deposition of amyloid-beta (Abeta) containing plaques and increases in the expression of cyclin-dependent kinase (CDK) enzymes. Chemical inhibition of CDKs prevents the neurotoxicity of the Abeta peptide. The activity of these kinases requires the binding of a cyclin component to the catalytic enzyme component. This study characterizes direct interactions between Abeta and cyclin B1. Abeta fragments containing the cytotoxic 31-35 region could inhibit biotinylated Abeta binding to cyclin B1. The same cytotoxic Abeta fragments all increased CDK-1 phosphorylation of known substrates in a cell free system. The CDK-1 inhibitor olomoucine prevented the cytotoxicity of Abeta 31-35 containing peptides in differentiated human teratocarcinoma cell line, Ntera 2/cl-D1 (NT-2) neurons. These direct interactions between cyclin B1 and Abeta provide potential mechanisms for the cytotoxicity of the Abeta peptide.

• Authors: Nathaniel G N Milton
• Journal: Neuroscience letters (Neurosci Lett) Vol. 322 Issue 2 Pg. 131-3 (Apr 05 2002) ISSN: 0304-3940 [Print] Ireland
• PMID: 11958860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• CCNB1 protein, human
• Cyclin B
• Cyclin B1
• Peptide Fragments
• amyloid beta-protein (31-35)
• CDC2 Protein Kinase

Topics

• Amino Acid Sequence
• Amyloid beta-Peptides (metabolism)
• CDC2 Protein Kinase (metabolism)
• Cyclin B (metabolism)
• Cyclin B1
• Humans
• Molecular Sequence Data
• Neurons (metabolism)
• Peptide Fragments (metabolism)
• Protein Binding
• Tumor Cells, Cultured