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J. Biol. Chem., Vol. 280, Issue 51, 41881-41892, December 23, 2005

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The Transcriptional Response of Saccharomyces cerevisiae to Pichia membranifaciens Killer Toxin^*

Antonio Santos, María del Mar Álvarez, Manuel San Mauro, Concepción Abrusci, and Domingo Marquina1

From the Department of Microbiology, Biology Faculty and the Department of Biochemistry and Molecular Biology, Medicine Faculty, Complutense University of Madrid, Madrid 28040, Spain

The transcriptional response of Saccharomyces cerevisiae to Pichia membranifaciens killer toxin (PMKT) was investigated. We explored the global gene expression responses of the yeast S. cerevisiae to PMKT using DNA microarrays, real time quantitative PCR, and Northern blot. We identified 146 genes whose expression was significantly altered in response to PMKT in a non-random functional distribution. The majority of induced genes, most of them related to the high osmolarity glycerol (HOG) pathway, were core environmental stress response genes, showing that the coordinated transcriptional response to PMKT is related to changes in ionic homeostasis. Hog1p was observed to be phosphorylated in response to PMKT implicating the HOG signaling pathway. Individually deleted mutants of both up- (99) and down-regulated genes (47) were studied for altered sensitivity; it was observed that the deletion of up-regulated genes generated hypersensitivity (82%) to PMKT. Deletion of down-regulated genes generated wild-type (36%), resistant (47%), and hypersensitive (17%) phenotypes. This is the first study that shows the existence of a transcriptional response to the poisoning effects of a killer toxin.

Received for publication, June 28, 2005 , and in revised form, September 12, 2005.

^* 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.

¹ To whom correspondence should be addressed. Tel./Fax: 34-91-394-49-64; E-mail: dommarq{at}bio.ucm.es.

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