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Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region
Journal article   Peer reviewed

Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region

Miles A PUFALL, Gregory M LEE, Mary L NELSON, Hyun-Seo KANG, Algirdas VELYVIS, Lewis E KAY, Lawrence P MCINTOSH and Barbara J GRAVES
Science (American Association for the Advancement of Science), Vol.309(5731), pp.142-145
2005
DOI: 10.1126/science.1111915
PMID: 15994560

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Abstract

Cell signaling that culminates in posttranslational modifications directs protein activity. Here we report how multiple $Ca^{2+}-dependent$ 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.
Molecular Genetics Fundamental and applied biological sciences. Psychology Biological and medical sciences Transcription. Transcription factor. Splicing. Rna processing Molecular and cellular biology

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