Journal article
Differential Regulation of Ceramide Synthase Components LAC1 and LAG1 in Saccharomyces cerevisiae
Eukaryotic cell, Vol.3(4), pp.880-892
08/2004
DOI: 10.1128/EC.3.4.880-892.2004
PMCID: PMC500886
PMID: 15302821
Abstract
ABSTRACT
In
Saccharomyces cerevisiae
, the essential ceramide synthase reaction requires the presence of one of a homologous pair of genes,
LAG1
and
LAC1
. Mutants that lack both of these genes cannot produce ceramide and exhibit a striking synthetic growth defect. While the regulation of ceramide production is critical for the control of proliferation and for stress tolerance, little is known of the mechanisms that ensure proper control of this process. The data presented here demonstrate that the pleiotropic drug resistance (Pdr) regulatory pathway regulates the transcription of multiple genes encoding steps in sphingolipid biosynthesis, including
LAC1
. The zinc cluster transcriptional activators Pdr1p and Pdr3p bind to Pdr1p/Pdr3p-responsive elements (PDREs) in the promoters of Pdr pathway target genes.
LAC1
contains a single PDRE in its promoter, but notably,
LAG1
does not. Reporter gene, Northern blot, and Western blot assays indicated that the expression level of Lac1p is approximately three times that of Lag1p. Detailed analyses of the
LAC1
promoter demonstrated that transcription of this gene is inhibited by the presence of the transcription factor Cbf1p and the anaerobic repressor Rox1p.
LAG1
transcription was also elevated in
cbf1
Δ cells, indicating at least one common regulatory input. Although a hyperactive Pdr pathway altered the profile of sphingolipids produced, the loss of either
LAC1
or
LAG1
alone failed to produce further changes. Two other genes involved in sphingolipid biosynthesis (
LCB2
and
SUR2
) were found to contain PDREs in their promoters and to be induced by the Pdr pathway. These data demonstrate extensive coordinate control of sphingolipid biosynthesis and multidrug resistance in yeast.
Details
- Title: Subtitle
- Differential Regulation of Ceramide Synthase Components LAC1 and LAG1 in Saccharomyces cerevisiae
- Creators
- Marcin Kolaczkowski - Wrocław Medical UniversityAnna Kolaczkowska - University of IowaBarbara Gaigg - University of FribourgRoger Schneiter - University of FribourgW. Scott Moye-Rowley - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Eukaryotic cell, Vol.3(4), pp.880-892
- DOI
- 10.1128/EC.3.4.880-892.2004
- PMID
- 15302821
- PMCID
- PMC500886
- NLM abbreviation
- Eukaryot Cell
- ISSN
- 1535-9778
- eISSN
- 1535-9786
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 08/2004
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984297601602771
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