کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2047545 1073989 2014 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A switch-like dynamic mechanism for the initiation of replicative senescence
ترجمه فارسی عنوان
مکانیزم پویایی سوئیچ برای شروع پیری تکراری
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
چکیده انگلیسی


• We model the correlation between telomere shortening and p53 activation.
• Three mechanisms contribute to telomere loss during cell replication.
• p53 is activated in a switch-like manner to induce replicative senescence.
• Senescence is triggered once the minimal telomere length reaches a threshold.
• The TRF2-ATM-p53-Siah1 positive feedback underlies the switching behavior of p53.

Telomeres are specialized structures protecting chromosomes against genome instability. Telomeres shorten with cell division, and replicative senescence is induced when telomeres are badly eroded. Whereas TRF2 (telomeric-repeat binding factor 2), ATM (ataxia telangiectasia mutated) and p53 have been identified involved in senescence induction, how it is triggered remains unclear. Here, we propose an integrated model associating telomere loss with senescence trigger. We characterize the dynamics of telomere shorting and the p53-centered regulatory network. We show that senescence is initiated in a switch-like manner when both the shortest telomere becomes uncapped and the TRF2-ATM-p53-Siah1 positive feedback loop is switched on. This work provides a coherent picture of senescence induction in terms of telomere shortening and p53 activation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: FEBS Letters - Volume 588, Issue 23, 28 November 2014, Pages 4369–4374
نویسندگان
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