Nuclear transporters can be viewed as taxis that move cargo across the nuclear envelope. On page 649, Plafker et al. report that importin-11, a nuclear transport receptor, may be an especially selective cabbie. Importin-11 transports UbcM2, a ubiquitin (Ub)-conjugating enzyme, but it does so only when the enzyme is charged with a Ub at its active site.
UbcM2 is an E2 enzyme, which works with E1 and E3 proteins to polyubiquitinate and tag proteins for degradation in the proteasome. To test whether importin-11 preferentially transports the Ub-charged UbcM2 or the unloaded enzyme, Plafker et al. performed coimmunoprecipitation assays with wild-type UbcM2, a mutant enzyme that is constitutively loaded with Ub, or a mutant that cannot be loaded. Importin-11 selectively bound the Ub-charged forms of UbcM2. Furthermore, in vitro pull-down assays showed that, if ATP or the E1 enzyme that loads Ub onto the UbcM2...