E3-ligases and deubiquitinating enzymes (DUBs) control ubiquitination and modulate protein turn-over as well as subcellular localization. Aberrant protein levels and their mislocalization are processes thought to be involved in the pathomechanisms leading to polyQ diseases. Using transcriptomic analysis, we will assess whether in cellular models the presence of a protein with an expanded polyQ stretch leads to alterations of DUB expression patterns. Subsequently, selected DUB candidates will be functionally analyzed through manipulation of expression (knock-down) or of activity (DUB inhibition). Effects of DUBs’ knock-down or inhibition will be evaluated based on cell viability, polyQ protein subcellular localization and aggregate formation.