The deubiquitinating enzyme Dot4p is involved in regulating nutrient uptake.
In yeast, several membrane-bound nutrient transporters have been shown to be regulated by the covalent attachment of ubiquitin, a signal for internalization and degradation. The yeast gene DOT4 encodes one of a family of enzymes which remove ubiquitin from proteins to which the peptide has been attached. Mutations in DOT4 cause a growth defect that is particularly severe when combined with mutations in nutrient biosynthetic enzymes (1). These results suggest that nutrient transport or utilization may be compromised in dot4 mutants. We now report that preventing the down-regulation by endocytosis of membrane proteins partially suppressed the dot4Delta growth defect. We also show that the activity of the amino acid permease Gap1p is reduced in DOT4 mutants. This correlates with a reduction in Gap1 protein level, while GAP1 mRNA levels remains unchanged. We conclude that Dot4p is involved in posttranscriptionally regulating Gap1p, and possibly other transporters as well.
Kahana
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Pritzker School of Medicine, University of Chicago, 924 East 57th Street, Chicago, Illinois, USA. kah7@midway.uchicago.edu
D026905:Amino Acid Transport Systems; D000596:Amino Acids / Q000378:metabolism; D002455:Cell Division; D015536:Down-Regulation; D004705:Endocytosis; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis; D029701:Saccharomyces cerevisiae Proteins; D043222:Ubiquitin Thiolesterase; D015003:Yeasts / Q000201:enzymology* / Q000378:metabolism
D026905:Amino Acid Transport Systems; D000596:Amino Acids; D005656:Fungal Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C403282:UBP10 protein, S cerevisiae; D043222:Ubiquitin Thiolesterase