Highlights • Insertions in USP25 and USP28 catalytic domains mediate their oligomerization • DUB activity of USP25, but not USP28, is inhibited by tetramerization • An autoinhibitory motif in USP25 blocks Ub binding, impairing its activity • Dimers of USP28, as well as dimers and tetramers of USP25, exist in cells Summary The evolutionarily related deubiquitinating enzymes (DUBs) USP25 and USP28 comprise an identical overall domain architecture but are functionally non-redundant: USP28...
