Mechanism of polyamine tolerance in yeast: novel regulators and insights |
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Authors: | Z Porat N Wender O Erez C Kahana |
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Institution: | (1) Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 76100, Israel |
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Abstract: | 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 agp2Δ cells, fes1Δ 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,
fes1Δ 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.
Received 31 July 2005; received after revision 7 October 2005; accepted 19 October 2005 |
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Keywords: | FES1 AGP2 YGL007W polyamines ornithine decarboxylase |
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