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.
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.
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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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.