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YB-1 Phosphorylation at Serine 209 Inhibits Its Nuclear Translocation

Ekaterina M Sogorina1, Ekaterina R Kim1,2, Alexey V Sorokin1,3

  • 1Group of Protein Biosynthesis Regulation, Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Russia.

International Journal of Molecular Sciences
|January 11, 2022
PubMed

Insights

Akt kinase phosphorylates YB-1 at serine 209, inhibiting its nuclear import. This finding reveals a new regulatory mechanism for YB-1 translocation, impacting cancer aggressiveness and drug resistance.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Y-box binding protein 1 (YB-1) is a key regulator of cellular processes like proliferation and migration.
  • Nuclear localization of YB-1 is linked to tumor aggressiveness and poor prognosis.
  • Phosphorylation at serine 102 (S102) is known to promote YB-1 nuclear import.

Purpose of the Study:

  • To investigate the role of Akt kinase in YB-1 regulation.
  • To identify novel posttranslational modifications affecting YB-1 nuclear translocation.
  • To elucidate the impact of YB-1 phosphorylation at serine 209 (S209) on its subcellular localization.

Main Methods:

  • In vitro kinase assays to determine Akt's phosphorylation targets on YB-1.
  • Site-directed mutagenesis and phosphomimetic substitutions (S209D) to study phosphorylation effects.
  • Cellular assays to assess YB-1 nuclear translocation and its regulation.

Main Results:

  • Akt kinase directly phosphorylates YB-1 at serine 209 (S209) in vitro.
  • S209 is located near the YB-1 nuclear localization signal.
  • Phosphorylation at S209 inhibits YB-1 nuclear translocation and blocks S102-mediated import.

Conclusions:

  • Akt-mediated phosphorylation of YB-1 at S209 represents a novel inhibitory mechanism for YB-1 nuclear import.
  • This regulatory pathway offers new insights into controlling YB-1 localization in cancer cells.
  • Targeting YB-1 phosphorylation could be a potential strategy to overcome multidrug resistance.
Keywords:
AktS102S209YB-1nuclear transportphosphorylation

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