Screening assays that allow for the identification of agents that modulate the activity of N-terminal acetylation of a polypeptide and the Doa10 branch of the N-end rule pathway are provided. Also provided are methods of using an agent that modulates the activity of N-terminal acetylation of a polypeptide and the Doa10 branch of the N-end rule pathway to increase or decrease protein degradation in a cell, and to modulate physiologic and pathologic associated with N-terminal acetylation of a polypeptide and the Doa10 branch of the N-end rule pathway.
