Jennifer H Johnston, 4818900 Presley Cir, Cerritos, CA 90703

5763212, Jun 9, 1998

Apr 6, 1995

8/417791

Alexander Varshavsky - La Canada Flintridge CA
Jennifer Johnston - Altadena CA

California Institute of Technology - Pasadena CA

C12P 2102
C12N 121
C12N 510

435 691

Disclosed herein is a heat-inducible N-degron module. A heat-inducible N-degron module is a protein or peptide bearing a destabilizing N-terminal amino acid residue which becomes a substrate of the N-end rule pathway only at a temperature high enough to result in at least partial unfolding of the protein. At this elevated (nonpermissive) temperature, the heat-inducible N-degron module (and any protein or peptide attached at its C-terminus) is rapidly degraded in a cell in which the N-end rule pathway is operative. Also disclosed are DNA and protein fusion constructs, methods for screening for additional heat-inducible N-degron modules and methods for using the disclosed heat-inducible N-degron modules. Also disclosed are methods for inhibiting the degradation of a protein bearing an N-degron in which a low molecular mass, cell penetrating ligand is prebound to the protein.