Genetics, Vol. 164, 1305-1321, August 2003, Copyright © 2003

Sit4 Phosphatase Is Functionally Linked to the Ubiquitin-Proteasome System

Thorsten Singera, Stefan Haefnera, Michael Hoffmanna, Michael Fischera, Julia Ilyinaa, and Wolfgang Hilta
a Institut für Biochemie, Universität Stuttgart, 70569 Stuttgart, Germany

Corresponding author: Wolfgang Hilt, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany., hilt{at}po.uni-stuttgart.de (E-mail)

Communicating editor: F. WINSTON

Using a synthetic lethality screen we found that the Sit4 phosphatase is functionally linked to the ubiquitin-proteasome system. Yeast cells harboring sit4 mutations and an impaired proteasome (due to pre1-1 pre4-1 mutations) exhibited defective growth on minimal medium. Nearly identical synthetic effects were found when sit4 mutations were combined with defects of the Rad6/Ubc2- and Cdc34/Ubc3-dependent ubiquitination pathways. Under synthetic lethal conditions, sit4 pre or sit4 ubc mutants formed strongly enlarged unbudded cells with a DNA content of 1N, indicating a defect in the maintenance of cell integrity during starvation-induced G1 arrest. Sit4-related synthetic effects could be cured by high osmotic pressure or by the addition of certain amino acids to the growth medium. These results suggest a concerted function of the Sit4 phosphatase and the ubiquitin-proteasome system in osmoregulation and in the sensing of nutrients. Further analysis showed that Sit4 is not a target of proteasome-dependent protein degradation. We could also show that Sit4 does not contribute to regulation of proteasome activity. These data suggest that both Sit4 phosphatase and the proteasome act on a common target protein.




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