Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Chen, J. et al.

Functional significance of type 1 insulin-like growth factor- mediated nuclear translocation of the insulin receptor substrate-1 and beta-catenin.

Previous work has shown that the transcriptional regulator beta-catenin can translocate to the nuclei when cells are stimulated with the type 1 insulin-like growth factor (IGF-1). We show by immunocoprecipitation and by confocal microscopy that beta-catenin binds to and co-localizes with the insulin receptor substrate-1 (IRS-1), a docking protein for both the insulin and the IGF-1 receptors. IRS-1 is required for IGF-1- mediated nuclear translocation of beta-catenin, resulting in the activation of the beta-catenin target genes. IGF-1- mediated nuclear translocation of beta-catenin is facilitated by the nuclear translocation of IRS-1. Both IRS-1 and beta-catenin are recruited to the cyclin D1 promoter, an established target for beta-catenin, but only IRS-1 is recruited to the ribosomal DNA (rDNA) promoter. UBF proteins (known to interact with both IRS-1 and beta-catenin) are also detectable in the cyclin D1 and rDNA promoters. These results indicate that IRS-1 (activated by the IGF-1 receptor) is one of several proteins that regulate the subcellular localization and activity of beta-catenin. The ability of IRS-1 to localize to both RNA polymerase II (with beta-catenin) and RNA polymerase I-regulated promoters suggest an explanation for the effect of IRS-1 on both cell growth in size and cell proliferation. This possibility is supported by the demonstration that enforced nuclear localization of IRS-1 causes nuclear translocation of beta-catenin and transformation of normal mouse embryo fibroblasts (colony formation in soft agar).[1]

References

Functional significance of type 1 insulin-like growth factor-mediated nuclear translocation of the insulin receptor substrate-1 and beta-catenin. Chen, J., Wu, A., Sun, H., Drakas, R., Garofalo, C., Cascio, S., Surmacz, E., Baserga, R. J. Biol. Chem. (2005) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.