Erica L Johnson

US Patent:

51224631, Jun 16, 1992

Filed:

May 17, 1990

Appl. No.:

7/525150

Inventors:

Alexander J. Varshavsky - Boston MA
Erica S. Johnson - Somerville MA
David K. Gonda - Quincy MA
Mark Hochstrasser - Somerville MA

Assignee:

Massachusetts Institute of Technology - Cambridge MA

International Classification:

C12N 1509
C12N 1562

US Classification:

4351723

Abstract:

This invention pertains to a method of metabolically destabilizing a protein or peptide of interest in vivo provided that the protein or peptide contains a second determinant of the N-end rule-based degradation signal and provided that another (targeting) protein or peptide can be identified that specifically interacts with the protein or peptide of interest. The methods of the invention comprise contacting the protein or peptide of interest with the targeting protein or peptide which contains a destabilizing amino-terminal amino acid according to the N-end rule of protein degradation but lacking a second determinant of the N-end rule-based degradation signal. Because nearly all proteins specifically interact with other proteins, this is a broadly applicable method for metabolically destabilizing a protein or peptide of interest in vivo.