Significant Role for p16INK4a in p53-Independent Telomere-Directed Senescence
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چکیده
منابع مشابه
Significant Role for p16INK4a in p53-Independent Telomere-Directed Senescence
Telomere attrition in primary human fibroblasts induces replicative senescence accompanied by activation of the p53 and p16(INK4a)/RB tumor suppressor pathways. Although the contribution of p53 and its target, p21, to telomere-driven senescence have been well established, the role of p16(INK4a) is controversial. Attempts to dissect the significance of p16(INK4a) in response to telomere shorteni...
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The p16(INK4A) (hereafter p16) tumor suppressor is encoded by the INK4A/ARF locus which is among the most commonly dysregulated sequences in human cancer. By inhibiting cyclin-dependent kinases, p16 activates the G1-S checkpoint, and this response is often considered to be critical for establishing a senescence-like growth arrest. Not all studies support a universal role for p16 in senescence. ...
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senescence is the activation of the INK4/ARF locus, which is epigenetically regulated and under tight control of the Polycomb group (PcG) Trithorax group (TrxG) proteins [1]. In proliferating cells, the locus is silenced by Polycomb repressive complexes (PRCs), and the chromatin is enriched in H3K27me3 [2]. Upon senescence triggers, PRCs are displaced and the repressive H3K27me3 mark is removed...
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p16(Ink4a) is a tumor suppressor and a marker for cellular senescence. Previous studies have shown that p16(Ink4a) plays an important role in the response to DNA damage signals caused by telomere dysfunction. In this study, we crossed Wrn(-/-) and p16(Ink4a-/-) mice to knock out the p16(Ink4a) function in a Wrn null background. Growth curves showed that loss of p16(Ink4a) could rescue the growt...
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ژورنال
عنوان ژورنال: Current Biology
سال: 2004
ISSN: 0960-9822
DOI: 10.1016/j.cub.2004.12.025