Inhibiting degradation of a degron-bearing protein

Details Inhibiting degradation of a degron-bearing protein Inhibiting degradation of a degron-bearing protein

1995-04-06

1998-06-09

Wax, Robert A.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

435 697, 4352523, 435325, C12P 2102, C12N 121, C12N 510

Patent

active

057632120

ABSTRACT:
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.

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Alberts et al. Molecular Biology of the Cell, Garland Publishing, NY, pp. 219-221, 1994.
Varshavsky, Alexander, "The N-End Rule", Cell 69: 725 (1992).
Matthews et al., J. Biol. Chem. 260: 392 (1985).

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