References and Notes

intracellular proteins, resulting in C-terminal fragments that often bear destabilizing N-terminal residues of the Ubr1-mediated branch of the N-end–rule pathway (fig. S1C). Such fragments are often short-lived in vivo, thereby regulating specific circuits [reviewed in (13)]. Given the major expansion of the N-end rule in the present work (Fig. 4), most in vivo–produced C-terminal fragments of intracellular proteins should now be viewed, a priori, as putative targets of the Doa10 or Ubr1 branches of the N-end–rule pathway. The topologically unique location of N-terminal residues, their massive involvement in proteolysis, and their extensive modification