title: Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and X-ray crystallography.
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.
authors: Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, London, United Kingdom.
authors: Edwin
authors: E
authors: Nkansah
authors: Rahi
authors: R
authors: Shah
authors: Gavin W
authors: GW
authors: Collie
authors: Gary N
authors: GN
authors: Parkinson
authors: Jonathan
authors: J
authors: Palmer
authors: Khondaker M
authors: KM
authors: Rahman
authors: Tam T
authors: TT
authors: Bui
authors: Alex F
authors: AF
authors: Drake
authors: Jarmila
authors: J
authors: Husby
authors: Stephen
authors: S
authors: Neidle
authors: Giovanna
authors: G
authors: Zinzalla
authors: David E
authors: DE
authors: Thurston
authors: Andrew F
authors: AF
authors: Wilderspin
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D050796:STAT3 Transcription Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D010748:Phosphopeptides; D050796:STAT3 Transcription Factor; D014443:Tyrosine; D004247:DNA