Abstract
The STAT3 transcription factor plays a central role in a wide range of cancer types where it is over-expressed. Previously, phosphorylation of this protein was thought to be a prerequisite for direct binding to DNA. However, we have now shown complete binding of a purified unphosphorylated STAT3 (uSTAT3) core directly to M67 DNA, the high affinity STAT3 target DNA sequence, by a protein electrophoretic mobility shift assay (PEMSA). Binding to M67 DNA was inhibited by addition of increasing concentrations of a phosphotyrosyl peptide. X-ray crystallography demonstrates one mode of binding that is similar to that known for the STAT3 core phosphorylated at Y705.
Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Binding, Competitive
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Circular Dichroism
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Crystallography, X-Ray
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DNA / chemistry*
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DNA / genetics
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DNA / metabolism*
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Electrophoretic Mobility Shift Assay / methods*
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Humans
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Models, Molecular
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Nucleic Acid Conformation
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Phosphopeptides / chemistry
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Phosphopeptides / metabolism
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Phosphorylation
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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STAT3 Transcription Factor / chemistry*
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism*
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Tyrosine / chemistry
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Tyrosine / genetics
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Tyrosine / metabolism
Substances
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Luminescent Proteins
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Phosphopeptides
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STAT3 Transcription Factor
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Tyrosine
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DNA