USP9X: Angelman sindromearen tratamendurako itu berria ote?

Abstract

UBE3A proteinaren gabeziak Angelman sindromea sortarazten du. Proteina honek zelulako beste proteina batzuk ubikuitinatzen ditu, beraien funtzioa erregulatuz. Hortaz, UBE3A falta denean, bere substratuak –DDI1 kasu– gutxiago ubikuitinatuko dira, ondorio larriak ekarriz. Horrez gain, deubikuitinasa deritzen proteinek substratuen ubikuitina kentzean, egoera larritzen da. Lan honetan DDI1 substratua deubikuitinatzen duen proteinetako bat –USP9X– identifikatu dugu eta diana terapeutiko gisa aurkeztu dugu, berau inhibitzeak DDI1 proteinaren ubikuitinazioa emendatu eta gaixotasunaren eredu diren eulien sintomatologia hobetzen baitu.

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.