Pellino-2 in nonimmune cells: novel interaction partners and intracellular localization

FEBS Lett. 2021 Dec;595(23):2909-2921. doi: 10.1002/1873-3468.14212. Epub 2021 Nov 12.


Pellino-2 is an E3 ubiquitin ligase that mediates intracellular signaling in innate immune pathways. Most studies of endogenous Pellino-2 have been performed in macrophages, but none in nonimmune cells. Using yeast two-hybrid screening and co-immunoprecipitation, we identified six novel interaction partners of Pellino-2, with various localizations: insulin receptor substrate 1, NIMA-related kinase 9, tumor necrosis factor receptor-associated factor 7, cyclin-F, roundabout homolog 1, and disheveled homolog 2. Pellino-2 showed cytoplasmic localization in a wide range of nonimmune cells under physiological potassium concentrations. Treatment with the potassium ionophore nigericin resulted in nuclear localization of Pellino-2, which was reversed by the potassium channel blocker tetraethylammonium. Live-cell imaging revealed intracellular migration of GFP-tagged Pellino-2. In summary, Pellino-2 interacts with proteins at different cellular locations, taking part in dynamic processes that change its intracellular localization influenced by potassium efflux.

Keywords: CYCLIN-F; DVL-2; IRS-1; NEK9; ROBO-1; TRAF7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Fibroblasts / metabolism
  • HEK293 Cells
  • Humans
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Interaction Maps
  • Two-Hybrid System Techniques
  • Ubiquitin-Protein Ligases / metabolism*


  • Nuclear Proteins
  • PELI2 protein, human
  • Ubiquitin-Protein Ligases