Ubiquilin-1 and protein quality control in Alzheimer disease.
Single nucleotide polymorphisms in the ubiquilin-1 gene may confer risk for late-onset Alzheimer disease (AD). We have shown previously that ubiquilin-1 functions as a molecular chaperone for the amyloid precursor protein (APP) and that protein levels of ubiquilin-1 are decreased in the brains of AD patients. We have recently found that ubiquilin-1 regulates APP trafficking and subsequent secretase processing by stimulating non-degradative ubiquitination of a single lysine residue in the cytosolic domain of APP. Thus, ubiquilin-1 plays a central role in regulating APP biosynthesis, trafficking and ultimately toxicity. As ubiquilin-1 and other ubiquilin family members have now been implicated in the pathogenesis of numerous neurodegenerative diseases, these findings provide mechanistic insights into the central role of ubiquilin proteins in maintaining neuronal proteostasis.
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX USA.
Amina
A
El Ayadi
Emily S
ES
Stieren
José M
JM
Barral
Darren
D
Boehning
D048868:Adaptor Proteins, Signal Transducing; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D021381:Protein Transport; D059748:Proteolysis
D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C107792:UBQLN1 protein, human
Alzheimer disease; amyloid precursor protein; molecular chaperone; trafficking; ubiquilin-1; ubiquitination