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SUMOylation Mediate...
SUMOylation Mediates the Nuclear Translocation and Signaling of the IGF-1 Receptor
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Sehat, Bita (author)
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- Tofigh, Ali (author)
- KTH,Beräkningsbiologi, CB
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- Lin, Yingbo (author)
- Karolinska Institutet
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- Trocme, Eric (author)
- Karolinska Institutet
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- Liljedahl, Ulrika (author)
- Uppsala universitet,Molekylär medicin
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- Lagergren, Jens (author)
- KTH,Beräkningsbiologi, CB
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- Larsson, Olle (author)
- Karolinska Institutet
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2010
- 2010
- English.
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In: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 3:108
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Subject headings
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- 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.
Keyword
- growth-factor receptor
- insulin-receptor
- tyrosine kinase
- i receptor
- chromatin immunoprecipitation
- transcription factor
- sumo-1
- modification
- proximity ligation
- egf receptor
- protein
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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