کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10905197 1086737 2005 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
CDK2 translational down-regulation during endothelial senescence
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
CDK2 translational down-regulation during endothelial senescence
چکیده انگلیسی
Here we report for the first time that loss of CDK2 activity, by translational inhibition and through CDK2 inhibition by p21Cip1/Waf1, may be responsible for endothelial senescence. We show that expression of dominant-negative p53 extends human umbilical vein endothelial cell (HUVEC) lifespan past senescence. HUVEC expressing telomerase can completely bypass senescence and become immortal (i-HUVEC). Surprisingly, early passage i-HUVEC, like senescent HUVEC, express high levels of the CDK inhibitors p16INK4a and p21Cip1/Waf1. Expression of p16INK4a can persist for over 280 population doublings, while p21Cip1/Waf1 expression was eventually lost in five of six i-HUVEC lines. Senescent HUVEC contain undetectable CDK2 activity, which results from a dramatic reduction of CDK2 protein levels and inhibition of remaining CDK2 by p21Cip1/Waf1. The decreased CDK2 levels in senescent HUVEC are not due to decreased transcription or protein stability; rather, CDK2 translation declines during senescence. Bypass of endothelial senescence by telomerase entails the restoration of CDK2 translation and activity. These results suggest that p16INK4a does not play a role in endothelial senescence. Rather, CDK2 translational down-regulation may be a key regulatory event in replicative senescence of endothelial cells. Understanding the mechanisms regulating endothelial senescence will be critical in determining the role of endothelial senescence in tumor growth.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 307, Issue 1, 1 July 2005, Pages 118-130
نویسندگان
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