Searching for Angelman syndrome therapeutical targets: deubiquitinase USP9X in the spotlight

Abstract

Lack of UBE3A protein causes Angelman syndrome. This protein is in charge of ubiquitinating other proteins in the cell. Therefore, when there is lack of UBE3A, its substrates —such as DDI1— will be less ubiquitinated, negatively affecting cell equilibrium. Moreover, proteins named deubiquitinases remove ubiquitin from the substrates, making the scenario even worse. In this work we have identified one of the proteins —USP9X— that deubiquitinates DDI1 and presented it as a therapeutical target, since its inhibition enhances DDI1 ubiquitination and improves the climbing ability of Angelman syndrome model flies.