Rsp5p ubiquitin ligase and the transcriptional activators Spt23p and Mga2p are involved in co-regulation of biosynthesis of end products of the mevalonate pathway and triacylglycerol in yeast Saccharomyces cerevisiae.
Rsp5p, a yeast S. cerevisiae ubiquitin ligase, is essential for regulation of unsaturated fatty acid synthesis via activation of the transcriptional activators Spt23p and Mga2p. Here we show that the conditional mutant rsp5-19 produces decreased levels of the end products of mevalonate pathway, such as ergosterol, ubiquinone and of dolichols, especially those with 19-24 isoprene units. The mechanism of Rsp5p involvement in the control of these lipid synthesis pathways was addressed by overproduction of Rsp5p-independent Spt23p or Mga2p. Expression of constitutively active forms of these transactivators resulted in excess production of ergosterol, but did not restore a wild-type level of dolichols. Moreover, synthesis of long chain dolichols was decreased in the wild-type and a rsp5-19 background. Finally, overproduction of active Spt23p or Mga2p was accompanied by the appearance of large lipid particles in the wild-type and rsp5-19 strains as observed by Nile Red staining, due to accumulation of unsaturated triacylglycerol. Thus, we conclude that Rsp5p, Spt23p and Mga2p may participate in the control of the homeostasis of lipids and lipid particles.
Kaliszewski
Paweł
P
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
Szkopińska
Anna
A
Ferreira
Thierry
T
Swiezewska
Ewa
E
Berges
Thierry
T
Zoładek
Teresa
T
D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways; D003594:Cytoplasmic Granules / Q000378:metabolism; D004122:Dimethylallyltranstransferase / Q000235:genetics / Q000378:metabolism; D004286:Dolichols / Q000096:biosynthesis; D056827:Endosomal Sorting Complexes Required for Transport; D004875:Ergosterol / Q000096:biosynthesis; D050356:Lipid Metabolism; D008565:Membrane Proteins; D008798:Mevalonic Acid / Q000378:metabolism*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014170:Transformation, Genetic; D014280:Triglycerides / Q000096:biosynthesis*; D014451:Ubiquinone / Q000096:biosynthesis; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism
D004286:Dolichols; D056827:Endosomal Sorting Complexes Required for Transport; D008565:Membrane Proteins; C087570:SPT23 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; D014451:Ubiquinone; D043743:Ubiquitin-Protein Ligase Complexes; D019883:Alkyl and Aryl Transferases; C511732:Srt1 protein, S cerevisiae; D004122:Dimethylallyltranstransferase; C485360:RER2 protein, S cerevisiae; C469287:RSP5 protein, S cerevisiae; D008798:Mevalonic Acid; D004875:Ergosterol