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Cell Growth and Development

Yeast Glycogen Synthase Kinase 3 Is Involved in Protein Degradation in Cooperation with Bul1, Bul2, and Rsp5

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Pages 6712-6720 | Received 08 Feb 2000, Accepted 09 Jun 2000, Published online: 28 Mar 2023
 

Abstract

The yeast Saccharomyces cerevisiae has four genes,MCK1, MDS1 (RIM11),MRK1, and YOL128c, that encode glycogen synthase kinase 3 (GSK-3) homologs. The gsk-3 null mutant, in which these four genes are disrupted, shows temperature sensitivity, which is suppressed by the expression of mammalian GSK-3β and by an osmotic stabilizer. Suppression of temperature sensitivity by an osmotic stabilizer is also observed in the bul1 bul2 double null mutant, and the temperature sensitivity of the bul1 bul2 double null mutant is suppressed by multiple copies of MCK1. We have screened rog mutants (revertants of gsk-3) which suppress the temperature sensitivity of the mck1 mds1 double null mutant and found that two of them,rog1 and rog2, also suppress the temperature sensitivity of the bul1 bul2 double null mutant. Bul1 and Bul2 have been reported to bind to Rsp5, a hect (for homologous to E6-associated-protein carboxyl terminus)-type ubiquitin ligase, but involvement of Bul1 and Bul2 in protein degradation has not been demonstrated. We find that Rog1, but not Rog2, is stabilized in the gsk-3 null and the bul1 bul2 double null mutants. Rog1 binds directly to Rsp5, and their interaction is dependent on GSK-3. Furthermore, Rog1 is stabilized in the npi1 mutant, in which RSP5 expression levels are reduced. These results suggest that yeast GSK-3 regulates the stability of Rog1 in cooperation with Bul1, Bul2, and Rsp5.

ACKNOWLEDGMENTS

We are grateful to B. André, A. Toh-e, Y. Kikuchi, K. Tanaka, and H. Yashiroda for donating plasmids and yeast strains. We also thank A. Toh-e, Y. Kikuchi, K. Tanaka, and H. Yashiroda for helpful discussion.

This work was supported by grants-in-aid for scientific research and for scientific research on priority areas from the Ministry of Education, Science, and Culture, Japan (1998, 1999), and by grants from the Yamanouchi Foundation for Research on Metabolic Disorders (1998, 1999) and the Uehara Memorial Foundation (1998).

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