کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815251 | 1058462 | 2014 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mig-6 participates in the regulation of cell senescence and retinoblastoma protein phosphorylation
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Mitogen-inducible gene-6 (Mig-6) is a cytosolic multiadaptor protein that is best known for its role as a negative feedback regulator of epidermal growth factor receptor (EGFR) mediated signalling. Alternative roles of Mig-6 are becoming increasingly recognised. Consistently with this, Mig-6 was demonstrated to be involved in a broad spectrum of cellular events including tumour suppression which may include the induction of cellular senescence. Here, we investigated the mechanisms of Mig-6 induced premature cell senescence. Endogenous Mig-6 is poorly expressed in young fibroblasts, whilst its expression rises in cells presenting with typical features of senescence. Overexpression of Mig-6 is sufficient to trigger premature cellular senescence of early passage diploid lung fibroblasts (WI-38). Interestingly, Mig-6 overexpression reduced retinoblastoma protein (pRb) phosphorylation at the inactivating Ser249/Thr252 sites. We also found that phosphorylation of these sites in pRb is increased in the presence of the B-Raf V600E oncogenic mutation. We further show that Mig-6 overexpression reduces B-Raf V600E mediated pRb inactivation and preserves pRb function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 26, Issue 9, September 2014, Pages 1870-1877
Journal: Cellular Signalling - Volume 26, Issue 9, September 2014, Pages 1870-1877
نویسندگان
Malgorzata Milewska, Walter Kolch,