Using gene silencing by siRNA transfection, we have identified a panel of DUBs that influence F508del-CFTR rescue by corrector VX-809. In particular, knockdown of USP13 results in decreased F508del-CFTR function. Therefore, these DUBs may have a protective role on F508del-CFTR by contrasting the process of ubiquitination that occurs even in the presence of the corrector. The researchers also found DUBs whose silencing amplifies mutant CFTR rescue. In this case, it needs to postulate a more indirect mechanism in which the DUB activity affects the expression/function of a regulator of F508del-CFTR processing.
A better knowledge of the mechanisms that limit mutant CFTR rescue can lead to improved therapeutic strategies. The research will continue in the project FFC#6/2019.