Engineering Iron Responses in Mammalian Cells by Signal-Induced Protein Proximity

ACS Synth Biol. 2017 Jun 16;6(6):921-927. doi: 10.1021/acssynbio.6b00255. Epub 2017 Feb 24.

Abstract

A new synthetic biology engineering strategy integrating chemical reactivity sensing and small molecule induced protein dimerization has been developed to generate artificial Fe2+ signaling circuitry to control tailored cellular events in mammalian cells. The dual function probe ABA-FE18 (Fe2+-sensing and protein dimerization) derived from ABA was developed and used to control gene activation, signal transduction, and cytoskeletal remodeling in response to Fe2+. This technology was utilized to design signal circuitry incorporating "AND" and "OR" biologic gates that enables mammalian cells to translate different combinations of Fe2+ and H2O2 signals into predefined biological outputs.

Keywords: abscisic acid; biologic gate; biosensor; cell signaling; chemically induced proximity; labile iron.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biosensing Techniques
  • Cell Line
  • Humans
  • Iron* / chemistry
  • Iron* / metabolism
  • Models, Molecular
  • Protein Multimerization / genetics
  • Recombinant Fusion Proteins / genetics*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / genetics*
  • Synthetic Biology / methods*

Substances

  • Recombinant Fusion Proteins
  • Iron