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Science 22 February 2008:
Vol. 319. no. 5866, pp. 1090 - 1092
DOI: 10.1126/science.1151903
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Reports

NADP Regulates the Yeast GAL Induction System

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

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

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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.
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The Interaction between an Acidic Transcriptional Activator and Its Inhibitor: THE MOLECULAR BASIS OF Gal4p RECOGNITION BY Gal80p.
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Progress in Metabolic Engineering of Saccharomyces cerevisiae.
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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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Science. ISSN 0036-8075 (print), 1095-9203 (online)