SILAM Quantitative Proteomic Profiles Protein Expression Changes In Adult Angelman Syndrome Mouse Model

Maternally-derived deletions or inactivating mutations of UBE3A at 15q11-q13cause Angelman syndrome（AS）,characterized by intellectual disability,motor deficits and speech impairment.We applied SILAM quantitative proteomic approache toexplore the signal pathway and protein expression changes that occur in vivo in the Ube3a^m-/p+mouse model at adult stages.We first discovered and validated the up-regulated ribosomal proteins（RPs）in adult AS mice using multiple quantitative mass spectrometry strategies,and further experiments verified that the regulation istranslation-dependent.While the accumulated RPs and increased rRNAs（18S,28S）promote the protein synthesis by phosphorylation of S6K and eIF2α,which triggers the ER stress represented by exacerbated UPR signaling.Our studies provide greatly expanded view of protein changes in AS mice and identify age-dependent effects of UBE3A in regulating ribosome biogenesis that might contribute to the onset of the disease.