title: Electrochemical detection of the Fc-STAT3 phosphorylation and STAT3-Fc-STAT3 dimerization and inhibition.
abstract: Signal transducer and activator of transcription 3 (STAT3) protein is involved in regulatory functions in cell proliferation, differentiation and survival, and is linked to cancer phenotype and tumorigenesis. Towards developing new methodologies for screening STAT3 interactions, the electrochemical method based on the use of redox active protein was proposed. The electrochemical signal, due to the redox (ferrocene)-labeled STAT3 protein immobilized on a gold surface, was modulated due to protein dimerization with the unlabeled STAT3 molecule. The dramatic decrease in current density from 2.7 μA cm(-2) to 0.5 μA cm(-2) was observed following the STAT3-ferrocene-STAT3 dimerization. The electrochemical approach was further extended for screening the potential dimerization inhibitors. Previously published potent salicylic acid derivatives were the most promising candidates for inhibition of STAT3 dimerization in this assay. We expect that other SH2-containing proteins may be monitored by the proposed electrochemical method.
authors.affiliation: Department of Chemistry, Oakland University, 2200 North Squirrel Road, Rochester, Michigan, USA 48309. martic@oakland.edu.
authors.forename: S
authors.initials: S
authors.lastname: Martic
authors.forename: M K
authors.initials: MK
authors.lastname: Rains
authors.forename: S
authors.initials: S
authors.lastname: Haftchenary
authors.forename: V M
authors.initials: VM
authors.lastname: Shahani
authors.forename: D
authors.initials: D
authors.lastname: Kraskouskaya
authors.forename: D P
authors.initials: DP
authors.lastname: Ball
authors.forename: P T
authors.initials: PT
authors.lastname: Gunning
authors.forename: H B
authors.initials: HB
authors.lastname: Kraatz
mesh_terms: D015374:Biosensing Techniques; D055808:Drug Discovery; D055664:Electrochemical Techniques; D005296:Ferrous Compounds / Q000737:chemistry*; D006801:Humans; D000075163:Metallocenes; D010766:Phosphorylation / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D005296:Ferrous Compounds; D000075163:Metallocenes; D050796:STAT3 Transcription Factor; C004998:ferrocene