Originally published In Press as doi:10.1074/jbc.M407264200 on October 22, 2004
J. Biol. Chem., Vol. 279, Issue 53, 55425-55432, December 31, 2004
Nuclear Localization Destabilizes the Stress-regulated Transcription Factor Msn2*
Erich Durchschlag
,
Wolfgang Reiter
,
Gustav Ammerer, and
Christoph Schüller¶
From the
Institute of Biochemistry and Molecular Cell Biology and Ludwig Boltzmann Forschungsstelle for Biochemistry, Max F. Perutz Laboratories, University and BioCenter of Vienna, A-1030 Vienna, Austria
The transcriptional program of yeast cells undergoes dramatic changes during the shift from fermentative growth to respiratory growth. A large part of this response is mediated by the stress responsive transcription factor Msn2. During glucose exhaustion, Msn2 is activated and concentrated in the nucleus. Simultaneously, Msn2 protein levels also drop significantly under this condition. Here we show that the decrease in Msn2 concentration is due to its increased degradation. Moreover, Msn2 levels are also reduced under chronic stress or low protein kinase A (PKA) activity, both conditions that cause a predominant nuclear localization of Msn2. Similar effects were found in msn5 mutant cells that block Msn2 nuclear export. To approximate the effect of low PKA activity on Msn2, we generated a mutant form with alanine substitutions in PKA phosphorylation sites. High expression of this Msn2 mutant is detrimental for growth, suggesting that the increased degradation of nuclear Msn2 might be necessary to adapt cells to low PKA conditions after the diauxic shift or to allow growth under chronic stress conditions.
Received for publication, June 29, 2004
, and in revised form, October 13, 2004.
* This work was supported by Austrian Science Fund (FWF) Grants P12015, P13493, and P14653 (to G. A. and the late H. Ruis). 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.
This article was selected as a Paper of the Week.
These authors contributed equally to this work.
Current address: Ludwig Baltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre, Meidling 4th Medical Dept., Hanusch Hospital, Heinrich Collin Str. 30, A-1140, Vienna.
¶ To whom correspondence and reprint requests should be addressed: Inst. of Biochemistry and Molecular Cell Biology, Max F. Perutz Laboratories, University and BioCenter of Vienna, Dr. Bohr-Gasse 9/5, A-1030 Vienna, Austria. Tel.: 43-1-4277-52815; Fax: 43-1-4277-9528; E-mail: Christoph.Schueller{at}univie.ac.at.

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Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.