Solution structure of the oncogenic MIEN1 protein reveals a thioredoxin-like fold with a redox-active motif

PLoS One. 2012;7(12):e52292. doi: 10.1371/journal.pone.0052292. Epub 2012 Dec 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Circular Dichroism
  • DNA-Binding Proteins
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Oxidation-Reduction
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Thioredoxins / chemistry*
  • Transcription Factors / chemistry*

Substances

  • DNA-Binding Proteins
  • MIER1 protein, human
  • Nuclear Proteins
  • Transcription Factors
  • Thioredoxins

Grant support

The work was supported by grants from National Science Council in Taiwan awarded to CHH (NSC99-2119-M-002-010), and partial grants to CHH (ERP-101R8600) from Excellent Research Projects of National Taiwan University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.