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Science 304 (5677): 1644-1647

Copyright © 2004 by the American Association for the Advancement of Science

Phospholipid Metabolism Regulated by a Transcription Factor Sensing Phosphatidic Acid

C. J. R. Loewen,1 M. L. Gaspar,2 S. A. Jesch,2 C. Delon,3 N. T. Ktistakis,3 S. A. Henry,2 T. P. Levine1*

Abstract: Cells regulate the biophysical properties of their membranes by coordinated synthesis of different classes of lipids. Here, we identified a highly dynamic feedback mechanism by which the budding yeast Saccharomyces cerevisiae can regulate phospholipid biosynthesis. Phosphatidic acid on the endoplasmic reticulum directly bound to the soluble transcriptional repressor Opi1p to maintain it as inactive outside the nucleus. After the addition of the lipid precursor inositol, this phosphatidic acid was rapidly consumed, releasing Opi1p from the endoplasmic reticulum and allowing its nuclear translocation and repression of target genes. Thus, phosphatidic acid appears to be both an essential ubiquitous metabolic intermediate and a signaling lipid.

1 Division of Cell Biology, Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK.
2 Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853–2703, USA.
3 Signalling Programme, Babraham Institute, Babraham, Cambridge CB2 4AT, UK.

* To whom correspondence should be addressed. E-mail: tim.levine{at}ucl.ac.uk

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Genome-wide Analysis Reveals Inositol, Not Choline, as the Major Effector of Ino2p-Ino4p and Unfolded Protein Response Target Gene Expression in Yeast.
S. A. Jesch, X. Zhao, M. T. Wells, and S. A. Henry (2005)
J. Biol. Chem. 280, 9106-9118
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Role of the Unfolded Protein Response Pathway in Secretory Stress and Regulation of INO1 Expression in Saccharomyces cerevisiae.
H. J. Chang, S. A. Jesch, M. L. Gaspar, and S. A. Henry (2004)
Genetics 168, 1899-1913
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