Identifying UBE3A substrates targeted for proteasome degradation in human cortical neurons and their pathological importance in Angelman Syndrome
UBE3A is a protein that labels other proteins for disposal. It is thought that accumulation of proteins that would normally be “trashed” causes the deficits in AS. Using stem cells generated from Angelman syndrome patients or stem cells genetically modified to behave like those of Angelman syndrome patients, Dr. Martin Doughty and colleagues will identify the proteins normally labeled by UBE3A for disposal, determine if loss of UBE3A causes accumulation of these proteins, and determine whether artificially increasing the amounts of these proteins in human neurons also causes them to behave like AS neurons.
The overall goal of this work is to identify the targets of UBE3A that are important for AS. These targets may be helpful indicators of UBE3A presence and/or function (biomarkers) and may themselves be potential targets for therapeutics.