Ubiquitin-Mediated Degradative Pathway Degrades the Extracellular but Not the Intracellular Form of Amyloid β-Protein Precursor

• Published in: Biochemical and biophysical research communications Vol. 203; no. 3; pp. 1731 - 1738
• Main Authors: Gregori, L., Bhasin, R., Goldgaber, D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.09.1994
• Subjects: Alzheimer Disease - metabolism; Amyloid beta-Protein Precursor - biosynthesis; Amyloid beta-Protein Precursor - isolation & purification; Amyloid beta-Protein Precursor - metabolism; Blotting, Western; Electrophoresis, Polyacrylamide Gel; Extracellular Space - metabolism; Humans; Intracellular Fluid - metabolism; Kinetics; Protein Binding; Recombinant Proteins - biosynthesis; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; Ubiquitins - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1994.2386

The presence of ubiquitin and ubiquitin conjugates has been detected in patients affected by neurodegenerative diseases such as Alzheimer′s disease. We investigated the role of ubiquitin in the degradation of amyloid β-protein precursor (APP) and its participation in the process of amyloid β-protein formation. APP was tested as a substrate for degradation, using both the extracellular and the intracellular forms of APP770, APP751 and APP695. The intracellular APP forms did not show appreciable ubiquitin-mediated degradation. In contrast, the three extracellular forms of APP were degraded in vitro by this proteolytic pathway, with similar degradation rates. Our results suggest a potential regulatory role for the ubiquitin-dependent degradation mechanism in the in vivo APP metabolic pathway.