A proteasomal partner goes missing in Angelman syndrome

Abstract

Loss-of-function mutations in the UBE3A ubiquitin ligase are associated with Angelman syndrome (AS), a severe neurologic disorder. A new study defines the role of mutations in an N-terminal “AZUL” domain as mediating direct binding to a proteasomal subunit and shows that this interaction is correlated with the ability of UBE3A to promote Wnt/-catenin signaling. These results provide new insights into a central biomolecule in AS and suggest that defects in Wnt/-catenin signaling may underlie some AS phenotypes.