SUMOylation mediates the nuclear translocation and signaling of the IGF-1 receptor

Sci Signal. 2010 Feb 9;3(108):ra10. doi: 10.1126/scisignal.2000628.


The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in developmental and cancer biology. Most of its biological effects have been ascribed to its tyrosine kinase activity, which propagates signaling through the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. Here, we report that IGF-1 promotes the modification of IGF-1R by small ubiquitin-like modifier protein-1 (SUMO-1) and its translocation to the nucleus. Nuclear IGF-1R associated with enhancer-like elements and increased transcription in reporter assays. The SUMOylation sites of IGF-1R were identified as three evolutionarily conserved lysine residues-Lys(1025), Lys(1100), and Lys(1120)-in the beta subunit of the receptor. Mutation of these SUMO-1 sites abolished the ability of IGF-1R to translocate to the nucleus and activate transcription but did not alter its kinase-dependent signaling. Thus, we demonstrate a SUMOylation-mediated mechanism of IGF-1R signaling that has potential implications for gene regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus*
  • Cell Nucleus / metabolism
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lysine / chemistry
  • MAP Kinase Signaling System
  • Melanoma / metabolism
  • Models, Biological
  • Mutation
  • Protein Conformation
  • Receptor, IGF Type 1 / metabolism*
  • Signal Transduction*
  • Skin Neoplasms / metabolism


  • Receptor, IGF Type 1
  • Lysine