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Sci. Signal., 9 February 2010
Vol. 3, Issue 108, p. ra10
[DOI: 10.1126/scisignal.2000628]

RESEARCH ARTICLES

SUMOylation Mediates the Nuclear Translocation and Signaling of the IGF-1 Receptor

Bita Sehat1, Ali Tofigh2*, Yingbo Lin1*, Eric Trocmé1, Ulrika Liljedahl3, Jens Lagergren2, and Olle Larsson1{dagger}

1 Department of Oncology and Pathology, Karolinska Institutet, Cancer Center Karolinska, R8:04, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
2 KTH Royal Institute of Technology, Computational Biology, Stockholm Bioinformatics Centre, SE-100 44 Stockholm, Sweden.
3 Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.

* These authors contributed equally to this work.

Abstract: 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—Lys1025, Lys1100, and Lys1120—in the β 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.

{dagger} To whom correspondence should be addressed. E-mail: Olle.Larsson{at}ki.se

Citation: B. Sehat, A. Tofigh, Y. Lin, E. Trocmé, U. Liljedahl, J. Lagergren, O. Larsson, SUMOylation Mediates the Nuclear Translocation and Signaling of the IGF-1 Receptor. Sci. Signal. 3, ra10 (2010).

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