Journal of Biological Chemistry
Volume 276, Issue 47, 23 November 2001, Pages 43548-43556
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LIPIDS AND LIPOPROTEINS
The Membrane Proteins, Spt23p and Mga2p, Play Distinct Roles in the Activation of Saccharomyces cerevisiae OLE1 Gene Expression: FATTY ACID-MEDIATED REGULATION OF Mga2p ACTIVITY IS INDEPENDENT OF ITS PROTEOLYTIC PROCESSING INTO A SOLUBLE TRANSCRIPTION ACTIVATOR*

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The Saccharomyces OLE1gene encodes the Δ-9 fatty acid desaturase, an enzyme that converts saturated fatty acyl-CoAs into cis-Δ-9 unsaturated fatty acids. OLE1 gene expression is regulated by unsaturated fatty acids, which repress transcription and destabilize the OLE1 mRNA. Expression of OLE1 is activated by N-terminal proteolytic fragments of two homologous endoplasmic reticulum membrane proteins, Spt23p and Mga2p. Disruption of either gene does not significantly affect cell growth or fatty acid metabolism; cells that contain null alleles of both genes, however, are unsaturated fatty acid auxotrophs. An analysis of spt23Δand mga2Δ strains shows that Spt23p and Mga2p differentially activate and regulate OLE1 transcription. In glucose-grown cells, both genes activate transcription to similar levels of activity. Expressed alone, Mga2p induces high levels of OLE1 transcription in cells exposed to cobalt or grown in glycerol-containing medium. Spt23p expressed alone activates OLE1 transcription to levels similar to those in wild type cells. OLE1 expression is strongly repressed by unsaturated fatty acids in spt23Δ or mga2Δ cells, under all growth conditions. To test if OLE1 expression is controlled by fatty acids at the level of membrane proteolysis, soluble N-terminal fragments of Spt23p and Mga2p that lack their membrane-spanning regions (Δtm) were expressed under the control of their native promoters in spt23Δ;mga2Δcells. Under those conditions, Mga2pΔtm acts as a powerful transcription activator that is strongly repressed by unsaturated fatty acids. By comparison, the Spt23pΔtm polypeptide weakly activates transcription and shows little regulation by unsaturated fatty acids. Co-expression of the two soluble fragments results in activation to levels observed with the Mga2pΔtm protein alone. The fatty acid repression of transcription under those conditions is attenuated by Spt23Δtm, however, suggesting that the two proteins may interact to modulate OLE1 gene expression.

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Published, JBC Papers in Press, September 13, 2001, DOI 10.1074/jbc.M107845200

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This work was supported by National Institutes of Health Grant GM45768 (to C. E. M.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

These authors contributed equally to this work.