کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2107635 1083690 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
p53-Dependent Translational Control of Senescence and Transformation via 4E-BPs
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
p53-Dependent Translational Control of Senescence and Transformation via 4E-BPs
چکیده انگلیسی

SummaryeIF4E, the mRNA 5′ cap-binding translation initiation factor, is overexpressed in numerous cancers and is implicated in mechanisms underlying oncogenesis and senescence. 4E-BPs (eIF4E-binding proteins) inhibit eIF4E activity, and thereby act as suppressors of eIF4E-dependent pathways. Here, we show that tumorigenesis is increased in p53 knockout mice that lack 4E-BP1 and 4E-BP2. However, primary fibroblasts lacking 4E-BPs, but expressing p53, undergo premature senescence and resist oncogene-driven transformation. Thus, the p53 status governs 4E-BP-dependent senescence and transformation. Intriguingly, the 4E-BPs engage in senescence via translational control of the p53-stabilizing protein, Gas2. Our data demonstrate a role for 4E-BPs in senescence and tumorigenesis and highlight a p53-mediated mechanism of senescence through a 4E-BP-dependent pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 16, Issue 5, 3 November 2009, Pages 439–446
نویسندگان
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