Cleavage of the pseudoprotease iRhom2 by the signal peptidase complex reveals an ER-to-nucleus signalling pathway_Dulloo et al

This work expands the understanding of the spectrum of functions of both rhomboid-like proteins and SPC. Not only do iRhoms regulate the trafficking and activity of other membrane proteins – what is now consider to be core roles for members of the rhomboid-like superfamily – but their unexpected cleavage by SPC allows them to have a parallel nuclear role in regulating gene expression. The findings also extend the understanding of SPC, a protease with a primary role of cleaving off signal peptides, and demonstrate its ability to modulate signalling by the cleavage of non-canonical substrates like iRhoms.