title: Solution structure of the oncogenic MIEN1 protein reveals a thioredoxin-like fold with a redox-active motif.
abstract: The novel tumor biomarker MIEN1, identified by representational difference analysis, is overexpressed in breast cancer and prostate cancer. MIEN1 is considered an oncogenic protein, because MIEN1 overexpression functionally enhances migration and invasion of tumor cells via modulating the activity of AKT. However, the structure and molecular function of MIEN1 is little understood. Here, we report the solution structure of MIEN1, which adopts a thioredoxin-like fold with a redox-active motif. Comparison of backbone chemical shifts showed that most of the residues for both oxidized and reduced MIEN1 possessed the same backbone conformation, with differences limited to the active motif and regions in proximity. The redox potential of this disulfide bond was measured as -225 mV, which compares well with that of disulfides for other thioredoxin-like proteins. Overall, our results suggest that MIEN1 may have an important regulatory role in phosphorylation of AKT with its redox potential.
authors.affiliation: Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan. andyhsu@ntu.edu.tw
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hsu
authors.forename: Tang-Long
authors.initials: TL
authors.lastname: Shen
authors.forename: Chi-Fon
authors.initials: CF
authors.lastname: Chang
authors.forename: Yu-Yung
authors.initials: YY
authors.lastname: Chang
authors.forename: Lin-Ya
authors.initials: LY
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004268:DNA-Binding Proteins; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000737:chemistry*; D014157:Transcription Factors / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; C470480:MIER1 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D013879:Thioredoxins