PubMed: 27325702

Title
Amyloid Precursor Protein (APP) May Act as a Substrate and a Recognition Unit for CRL4CRBN and Stub1 E3 Ligases Facilitating Ubiquitination of Proteins Involved in Presynaptic Functions and Neurodegeneration.
Journal
The Journal of biological chemistry
Volume
291
Issue
None
Pages
17209-27
Date
2016-08-12
Authors
D'Adamio L | Del Prete D | Rajadhyaksha AM | Rice RC

Evidence 767e0b86ad

the ACR (APP cytosolic region) interacts with the E3 ubiquitin-protein ligases Stub1, which binds the NH2 terminus of the ACR, and CRL4(CRBN), which is formed by Cul4a/b, Ddb1, and Crbn, and interacts with the COOH terminus of the ACR via Crbn.

Evidence 359fee334b

As reported in Table 6, several brain-derived proteins associated with the ACR bait were ubiquitinated. These proteins can be separated into four groups as follows: (a) group 1, proteins of the ubiquitin-conjugating system; (b) group 2, presynaptic proteins; (c) group 3, other proteins implicated in AD; and (d) group 4, phosphorylation-dependent ACR interactors.

Evidence 973dbc3703

Together with the evidence that CRBN and CUL4B are linked to intellectual disability suggests a pathogenic mechanism, in which APP acts as a modulator of E3 ubiquitin-protein ligase(s).

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