The amyloid-beta peptide binds to cyclin B1 and increases human cyclin-dependent kinase-1 activity.
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.
Milton
Nathaniel G N
NG
Department of Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, London, UK. nmilton@rfc.ucl.ac.uk
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D010446:Peptide Fragments; C113042:amyloid beta-protein (31-35); D016203:CDC2 Protein Kinase