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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


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