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J. Biol. Chem. 275 (50): 39403-39410

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

Ubiquitin-mediated Proteolysis of a Short-lived Regulatory Protein Depends on Its Cellular Localization*

Uwe Lenk and Thomas SommerDagger

From the Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, Berlin 13092, Germany

In this study we demonstrate that the Deg1 degradation signal of the transcriptional repressor Matalpha 2 confers compartment-specific turnover to a reporter protein. Rapid degradation of a Deg1-containing fusion protein is observed only when the reporter is efficiently imported into the nucleus. In contrast, a reporter that is constantly exported from the nucleus exhibits an extended half-life. Furthermore, nuclear import functions are crucial for both Deg1-induced degradation as well as for the turnover of the endogenous Matalpha 2 protein. The conjugation of ubiquitin to a Deg1-containing reporter protein is abrogated in mutants affected in nuclear import. Obviously, the Deg1 signal initiates rapid proteolysis within the nucleoplasm, whereas in the cytosol it mediates turnover via a slower pathway. In both pathways the ubiquitin-conjugating enzymes Ubc6p/Ubc7p play a pivotal role. These observations imply that both the cellular targeting of a substrate and the compartment-specific activity of components of the ubiquitin-proteasome system define the half-life of naturally short-lived proteins.

* This work was partially supported by grants from the Deutsche Forschungsgemeinschaft and the Deutsch-Israelische Projektko-operation (to T. S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed. E-mail: tsommer@mdc-berlin.de.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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