Interferon Beta Activity Is Modulated via Binding of Specific S100 Proteins

Alexey S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Alexander I. Denesyuk, Evgenia I. Deryusheva, Victoria A. Rastrygina, Andrey S. Sokolov, Maria E. Permyakova, Ekaterina A. Litus, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Interferon-β (IFN-β) is a pleiotropic cytokine used for therapy of multiple sclerosis, which is also effective in suppression of viral and bacterial infections and cancer. Recently, we reported a highly specific interaction between IFN-β and S100P lowering IFN-β cytotoxicity to cancer cells (Int J Biol Macromol. 2020; 143: 633–639). S100P is a member of large family of multifunctional Ca 2+-binding proteins with cytokine-like activities. To probe selectivity of IFN-β—S100 interaction with respect to S100 proteins, we used surface plasmon resonance spectroscopy, chemical crosslinking, and crystal violet assay. Among the thirteen S100 proteins studied S100A1, S100A4, and S100A6 proteins exhibit strictly Ca 2+-dependent binding to IFN-β with equilibrium dissociation constants, K d, of 0.04–1.5 µM for their Ca 2+-bound homodimeric forms. Calcium depletion abolishes the S100—IFN-β interactions. Monomerization of S100A1/A4/A6 decreases K d values down to 0.11–1.0 nM. Interferon-α is unable of binding to the S100 proteins studied. S100A1/A4 proteins inhibit IFN-β-induced suppression of MCF-7 cells viability. The revealed direct influence of specific S100 proteins on IFN-β activity uncovers a novel regulatory role of particular S100 proteins, and opens up novel approaches to enhancement of therapeutic efficacy of IFN-β.

Original languageEnglish
Article number9473
Pages (from-to)1-23
JournalInternational Journal of Molecular Sciences
Volume21
Issue number24
DOIs
Publication statusPublished - 2020
MoE publication typeA1 Journal article-refereed

Keywords

  • S100 protein
  • cancer

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