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Science 319 (5866): 1090-1092

Copyright © 2008 by the American Association for the Advancement of Science

NADP Regulates the Yeast GAL Induction System

P. Rajesh Kumar,1 Yao Yu,2 Rolf Sternglanz,2 Stephen Albert Johnston,3 Leemor Joshua-Tor1*

Abstract: Transcriptional regulation of the galactose-metabolizing genes in Saccharomyces cerevisiae depends on three core proteins: Gal4p, the transcriptional activator that binds to upstream activating DNA sequences (UASGAL); Gal80p, a repressor that binds to the carboxyl terminus of Gal4p and inhibits transcription; and Gal3p, a cytoplasmic transducer that, upon binding galactose and adenosine 5'-triphosphate, relieves Gal80p repression. The current model of induction relies on Gal3p sequestering Gal80p in the cytoplasm. However, the rapid induction of this system implies that there is a missing factor. Our structure of Gal80p in complex with a peptide from the carboxyl-terminal activation domain of Gal4p reveals the existence of a dinucleotide that mediates the interaction between the two. Biochemical and in vivo experiments suggests that nicotinamide adenine dinucleotide phosphate (NADP) plays a key role in the initial induction event.

1 Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY11724, USA.
2 Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794–5215, USA.
3 Center for Innovations in Medicine, Biodesign Institute, School of Life Sciences, Arizona State University, Post Office Box 875901, Tempe, AZ 85287–5901, USA.

* To whom correspondence should be addressed. E-mail: leemor{at}cshl.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Effect of Ligand Binding on the Galactokinase Activity of Yeast Gal1p and Its Ability to Activate Transcription.
C. A. Sellick, T. A. Jowitt, and R. J. Reece (2009)
J. Biol. Chem. 284, 229-236
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The Interaction between an Acidic Transcriptional Activator and Its Inhibitor: THE MOLECULAR BASIS OF Gal4p RECOGNITION BY Gal80p.
J. B. Thoden, L. A. Ryan, R. J. Reece, and H. M. Holden (2008)
J. Biol. Chem. 283, 30266-30272
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Progress in Metabolic Engineering of Saccharomyces cerevisiae.
E. Nevoigt (2008)
Microbiol. Mol. Biol. Rev. 72, 379-412
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Dinucleotide-Sensing Proteins: Linking Signaling Networks and Regulating Transcription.
H. K. Lamb, D. K. Stammers, and A. R. Hawkins (2008)
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