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High-affinity interaction between interleukin-11 and S100P protein.

Alexei S Kazakov1, Andrei S Sokolov1, Victoria A Rastrygina1

  • 1Institute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya Str. 7, Pushchino, Moscow Region, 142290, Russia.

Biochemical and Biophysical Research Communications
|November 10, 2015
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Summary

Interleukin-11 (IL-11) and S100P proteins interact under physiological conditions, suggesting a role in cancer. This specific interaction may be a target for novel cancer therapies.

Keywords:
CancerInterleukinProtein–protein interactionS100 proteinSTAT3

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Interleukin-11 (IL-11) and S100P are oncoproteins frequently co-expressed in various cancers.
  • Their co-expression suggests a potential functional interaction during cancer development (oncogenesis).

Purpose of the Study:

  • To investigate the interaction between Interleukin-11 (IL-11) and S100P.
  • To characterize the binding affinity and conditions of this interaction.

Main Methods:

  • Surface plasmon resonance spectroscopy
  • Intrinsic fluorescence
  • Chemical crosslinking
  • Cell-based assays using HEK293 cells

Main Results:

  • Recombinant IL-11 and S100P were found to interact under physiological calcium ion concentrations.
  • IL-11 possesses at least two binding sites for S100P, with dissociation constants of 32 nM and 288 nM.
  • S100P binding affinity to IL-11 is 5-13 fold lower than IL-11's affinity for its receptor subunit alpha.
  • S100P did not affect IL-11-induced STAT3 activation in HEK293 cells but may influence other oncogenic pathways.

Conclusions:

  • A specific interaction between IL-11 and S100P occurs under physiologically relevant conditions.
  • This IL-11 - S100P interaction warrants consideration in the development of anti-cancer drugs targeting IL-11 signaling pathways.