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Open Access Green as soon as Postprint is submitted to ZB.
NBS1 is required for IGF-1 induced cellular proliferation through the Ras/Raf/MEK/ERK cascade.
Cell. Signal. 20, 2276-2285 (2008)
NBS1 is a member of the Mre11-Rad50-NBS1 complex, which plays a role in cellular responses to DNA damage and the maintenance of genomic stability. Transgenic mice models and clinical symptoms of NBS patients have shown that NBS1 exerts pleiotropic actions on the growth and development of mammals. The present study showed that after repression of endogenous NBS1 levels using short interfering RNA, hTERT-RPE cells demonstrated impaired proliferation and a poor response to IGF-1. NBS1 down-regulated cells displayed disturbances in periodical oscillations of cyclin E and A and delayed cell cycle progression. Remarkably, lower phosphorylation levels of c-Raf and diminished activity of Erk1/2 in response to IGF-1 suggest a link among NBS1, IGF-1 signaling and the Ras/Raf/MEK/ERK cascade. The functional relevance of NBS1 in mitogenic signaling and initiation of cell cycle progression were demonstrated in NBS1 down-regulated cells where IGF-1 had a limited ability to induce the FOS and CCND1 expressions. In conclusion, our findings provide strong evidence that NBS1 has a functional role in IGF-1 signaling for the promotion of cell proliferation via the Ras/Raf/MEK/ERK cascade.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
NBS1; Ras/Raf/MEK/ERK; MAPK; IGF-1; Cell cycle progression
ISSN (print) / ISBN
0898-6568
e-ISSN
0898-6568
Journal
Cellular Signalling
Quellenangaben
Volume: 20,
Issue: 2,
Pages: 2276-2285
Publisher
Elsevier
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Radiation Biology (ISB)