APC/CCdh1 specific degradation of Hsl1 and Clb2 is required for proper stress responses of S. cerevisiae

Kobi J. Simpson-Lavy, Julia Sajman, Drora Zenvirth, Michael Brandeis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Cdh1 activates the Anaphase Promoting Complex/Cyclosome (APC/C Cdh1) throughout G1 to degrade key cell cycle proteins. Cdh1 is not essential for cell proliferation, in spite of the fact that overexpression of some its degradation substrates is highly toxic. We report here that cdh1Δ cells are sensitive to stresses that activate the CWI (Cell Wall Integrity) and Hog1 MAP kinase pathways. Stresses did not activate APC/CCdh1 and cellular sensitivity was thus clearly due to constitutively elevated substrate levels. To explore the contribution of stabilization of individual APC/CCdh1 substrates to stress sensitivity, we generated cell lines expressing stabilized substrate mutants under their endogenous promoters. Cells expressing stabilized Hsl1 were sensitive to caffeine and failed to activate the Slt2 pathway. Cells expressing partially stable Clb2 were particularly sensitive to different stresses, possibly due to reduced Sic1 levels. Cells expressing stabilized Cdc5 were much less stress sensitive. Interestingly sensitivity of cdh1Δ cells does not seem to be restricted to G1 but is manifested also during S and G2 when the APC/CCdh1 is inactive anyway. We thus hypothesize that a role of G1 specific APC/CCdh1 activity is to reset substrate levels to enables appropriate regulation of substrate accumulation in the subsequent phases of the cell cycle.

Original languageAmerican English
Pages (from-to)3006-3012
Number of pages7
JournalCell Cycle
Volume8
Issue number18
DOIs
StatePublished - 15 Sep 2009

Bibliographical note

Funding Information:
We would like to thank A. Amon, D. Kellogg, F. Cross, W. Zachariae, M. Solomon and S. Sedgwick for yeast strains. We are grateful for antibodies and many fruitful discussions and for technical assistance to all the members of the Tzfati, Engelberg and Brandeis lab, in particular D. Engelberg, O. Feine Y. Cinnamon, Y. Lavy and S.S. Creat. This project was funded by grants from the Israel Science foundation (ISF 598/02), the Association for International Cancer research (AICR 05-012) and the Israel Cancer Research Foundation (ICRF).

Keywords

  • Cdc5
  • Cell wall integrity
  • Clb2
  • Hsl1
  • Slt2

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