Mechanism of polyamine tolerance in yeast: novel regulators and insights.
Polyamines are small charged molecules essential for various cellular functions, but at high levels they are cytotoxic. Two yeast kinases, SKY1 and PTK2, have been demonstrated to regulate polyamine tolerance. Here we report the identification and characterization of additional genes involved in regulating polyamine tolerance: YGL007W, FES1 and AGP2. Deletion of YGL007W, an open reading frame located within the promoter of the membrane proton pump PMA1, decreased Pma1p expression. Deletion of FES1 or AGP2 resulted in reduced polyamine uptake. While high-affinity spermine uptake was practically absent in agp2Delta cells, fes1Delta cells displayed only reduced affinity towards spermine. Despite the reduced uptake, the resistant strains accumulated significant levels of polyamines and displayed increased ornithine decarboxylase activity, suggesting reduced polyamine sensing. Interestingly, fes1Delta cells were highly sensitive to salt ions, suggesting different underlying mechanisms. These results indicate that mechanisms leading to polyamine tolerance are complex, and involve components other than uptake.
Porat
Z
Z
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Wender
N
N
Erez
O
O
Kahana
C
C
D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D018021:Lithium Chloride / Q000378:metabolism / Q000494:pharmacology; D016366:Open Reading Frames / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012965:Sodium Chloride / Q000378:metabolism / Q000494:pharmacology; D013096:Spermine / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
C402286:Agp2 protein, S cerevisiae; D026905:Amino Acid Transport Systems; C507801:FES1 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D027981:Symporters; D013096:Spermine; D012965:Sodium Chloride; D018021:Lithium Chloride