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Published March 24, 1989 | public
Journal Article

The degradation signal in a short-lived protein


Our previous work has shown that the amino-terminal residue of a short-lived protein is a distinct component of the protein's degradation signal. To define the complete signal, otherwise identical dihydrofolate reductase test proteins bearing different extensions and either a "stabilizing" or a "destabilizing" amino-terminal residue were expressed in the yeast S. cerevisiae and their in vivo half-lives compared. The amino-terminal degradation signal is shown to comprise two distinct determinants. One, discovered previously, is the protein's amino-terminal residue. The second determinant, identified in the present work, is a specific lysine residue whose function in the degradation signal is not dependent on the unique amino acid sequences in the vicinity of the residue. The mechanistic significance of the second determinant is illuminated by the finding that in a targeted, short-lived protein, a chain of branched ubiquitin-ubiquitin conjugates is confined to a lysine residue that has been identified in the present work as the second determinant of the degradation signal.

Additional Information

© 1989 Cell Press. Received 2 December 1988, Revised 26 January 1989. We are indebted to Daniel Finley for helpful discussions and advice throughout this work. We thank Michael Lanzer and Hermann Bujard for the DHFR expression vectors, Gottfried Schatz for the antibody to DHFR, members of this laboratory, especially David Gonda, Daniel Finley, Mark Hochstrasser, Bonnie Bartel, John McGrath, and John Tobias for their comments on the manuscript, and Barbara Doran for secretarial assistance. This work was supported by grants to A. V. from the National Institutes of Health (GM31530 and DK39520). A. B. was a Fellow of the European Molecular Biology Organization. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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