Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and X-ray crystallography

Edwin Nkansah; Rahi Shah; Gavin W. Collie; Gary N. Parkinson; Jonathan Palmer; Khondaker Rahman; Tam T. Bui; Alex F. Drake; Jarmila Husby; Stephen Neidle; Giovanna Zinzalla; David E Thurston; Andrew F. Wilderspin

doi:10.1016/j.febslet.2013.01.065

Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and X-ray crystallography

Edwin Nkansah, Rahi Shah, Gavin W. Collie, Gary N. Parkinson, Jonathan Palmer, Khondaker Rahman, Tam T. Bui, Alex F. Drake, Jarmila Husby, Stephen Neidle, Giovanna Zinzalla, David E Thurston, Andrew F. Wilderspin

Institute of Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

64 Citations (Scopus)

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.

Original language	English
Pages (from-to)	833-839
Number of pages	7
Journal	FEBS Letters
Volume	587
Issue number	7
DOIs	https://doi.org/10.1016/j.febslet.2013.01.065
Publication status	Published - 2 Apr 2013

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10.1016/j.febslet.2013.01.065

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Nkansah, E., Shah, R., Collie, G. W., Parkinson, G. N., Palmer, J., Rahman, K., Bui, T. T., Drake, A. F., Husby, J., Neidle, S., Zinzalla, G., Thurston, D. E., & Wilderspin, A. F. (2013). Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and X-ray crystallography. FEBS Letters, 587(7), 833-839. https://doi.org/10.1016/j.febslet.2013.01.065

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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.",

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AU - Shah, Rahi

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AU - Parkinson, Gary N.

AU - Palmer, Jonathan

AU - Rahman, Khondaker

AU - Bui, Tam T.

AU - Drake, Alex F.

AU - Husby, Jarmila

AU - Neidle, Stephen

AU - Zinzalla, Giovanna

AU - Thurston, David E

AU - Wilderspin, Andrew F.

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AB - 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.

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DO - 10.1016/j.febslet.2013.01.065

M3 - Article

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JO - FEBS Letters

JF - FEBS Letters

IS - 7

ER -

Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and X-ray crystallography

Abstract

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