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Science 309 (5731): 142-145

Copyright © 2005 by the American Association for the Advancement of Science

Variable Control of Ets-1 DNA Binding by Multiple Phosphates in an Unstructured Region

Miles A. Pufall,1 Gregory M. Lee,2 Mary L. Nelson,1 Hyun-Seo Kang,2 Algirdas Velyvis,3 Lewis E. Kay,3 Lawrence P. McIntosh,2 Barbara J. Graves1*

Abstract: Cell signaling that culminates in posttranslational modifications directs protein activity. Here we report how multiple Ca2+-dependent phosphorylation sites within the transcription activator Ets-1 act additively to produce graded DNA binding affinity. Nuclear magnetic resonance spectroscopic analyses show that phosphorylation shifts Ets-1 from a dynamic conformation poised to bind DNA to a well-folded inhibited state. These phosphates lie in an unstructured flexible region that functions as the allosteric effector of autoinhibition. Variable phosphorylation thus serves as a "rheostat" for cell signaling to fine-tune transcription at the level of DNA binding.

1 Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112–5550, USA.
2 Department of Biochemistry and Molecular Biology, Department of Chemistry, and The Michael Smith Laboratory, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
3 Departments of Medical Genetics, Biochemistry, and Chemistry, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.

* To whom correspondence should be addressed. E-mail: Barbara.Graves{at}hci.utah.edu


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