کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1931971 | 1050569 | 2010 | 6 صفحه PDF | دانلود رایگان |

The insulin receptor substrate (IRS) proteins are major substrates of both insulin receptor and insulin-like growth factor (IGF)-I receptor tyrosine kinases. Previously, we reported that IRS-3 is localized to both cytosol and nucleus, and possesses transcriptional activity. In the present study, we identified Bcl-3 as a novel binding protein to IRS-3. Bcl-3 is a nuclear protein, which forms a complex with the homodimer of p50 NF-κB, leading to enhancement of transcription through p50 NF-κB. We found that Bcl-3 interacts with the pleckstrin homology domain and the phosphotyrosine binding domain of IRS-3, and that IRS-3 interacts with the ankyrin repeat domain of Bcl-3. In addition, IRS-3 augmented the binding activity of p50 to the NF-κB DNA binding site, as well as the tumor necrosis factor (TNF)-α-induced transcriptional activity of NF-κB. Lastly, IRS-3 enhanced NF-κB-dependent anti-apoptotic gene induction and consequently inhibited TNF-α-induced cell death. This series of results proposes a novel function for IRS-3 as a transcriptional regulator in TNF-α signaling, distinct from its function as a substrate of insulin/IGF receptor kinases.
Journal: Biochemical and Biophysical Research Communications - Volume 394, Issue 3, 9 April 2010, Pages 697–702