Identification of nucleolar protein NOM1 as a novel nuclear IGF1R-interacting protein

Ravid Solomon-Zemler, Yair Pozniak, Tamar Geiger, Haim Werner

Research output: Contribution to journalArticlepeer-review

Abstract

The insulin-like growth factor-1 receptor (IGF1R) mediates the biological actions of both IGF1 and IGF2. In recent years, evidence has accumulated showing that, in addition to its classical cell-surface distribution, IGF1R translocates to cell nucleus via an apparently SUMO-1-dependent mechanism. While the role of IGF1R in nucleus has not yet been settled, available information suggests that the nuclear receptor displays activities usually linked to transcription factors, including DNA binding and transcription regulation. To gain insight into the biological pathways associated with nuclear IGF1R action we conducted a mass spectrometry-based proteomic analysis aimed at identifying interactors of IGF1R in nucleus of both benign and malignant breast cells. The nucleolar NOM1 molecule belongs to a family of proteins that contain the middle domain of eukaryotic initiation factor 4G (MIF4G) and/or interaction module (MA3), and functions in translation, cell growth and proliferation. Using a combination of co-immunoprecipitation and silencing assays we provide evidence of a complex, bi-directional interplay between nuclear IGF1R and nucleolar protein NOM1. Inhibition of nuclear IGF1R translocation by dansylcadaverine reduced NOM1 levels in nuclei of MCF7 cells. On the other hand, IGF1R overexpression enhanced NOM1 levels in the nuclear fraction. Of interest, NOM1 silencing led to a major increase in IGF1R biosynthesis. In summary, results are consistent with a physiologically-relevant interplay between the nuclear IGF1 signaling pathway and nucleolar protein NOM1.

Original languageEnglish
Pages (from-to)259-265
Number of pages7
JournalMolecular Genetics and Metabolism
Volume126
Issue number3
DOIs
StatePublished - Mar 2019

Keywords

  • IGF1 receptor
  • Insulin-like growth factor-1 (IGF1)
  • NOM1
  • Nuclear translocation
  • Proteomics

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