Identification of C-terminal extensions that protect proteins from intracellular proteolysis.

Revertants of defective mutants in the Arc repressor of bacteriophage P22 were isolated. Five of the six reverting mutations were frameshifts near the end of the coding sequence which resulted in proteins with C-terminal extensions. Each of the reverting mutations prolong the half-lives in vivo of the proteins in which they reside, yet they do not alter the thermodynamic stability, structure, oligomeric form, or DNA-binding properties of these proteins. Fusion of one of these tails to the C-terminal end of a mutant form of the N-terminal domain of lambda repressor also prevented proteolysis of this protein. These C-terminal sequences may prevent degradation by blocking the recognition of unstable proteins by the proteolytic machinery in the cell.