B-MYB 通过抑制 p16（INK4α）转录来延缓细胞衰老。
B-MYB delays cell aging by repressing p16 (INK4α) transcription.
机构信息
Peking University Research Center on Aging, Peking University Health Science Center, Beijing, People's Republic of China.
出版信息
Cell Mol Life Sci. 2011 Mar;68(5):893-901. doi: 10.1007/s00018-010-0501-9. Epub 2010 Aug 25.
Abstract
p16 ( INK4α ), an inhibitor of cyclin-dependent kinase 4 and 6, has been proposed to play an important role in cellular aging and in premature senescence. The expression of the p16 ( INK4α ) is primarily under transcriptional control. Our previous data showed that a negative regulation element lies in its promoter. In that element, a MYB-binding site (MBS) was uncovered by transcription analysis. Here, we report that MBS is a negative regulation element and B-MYB binds to this site in vivo. In human embryonic lung fibroblast cells, B-MYB downregulated p16 ( INK4α ) expression, whereas knocking down of B-MYB upregulated it. Evidence also showed that overexpression of B-MYB in cells could increase the number of utmost passage and decrease G1 block, whereas knocking down of B-MYB could impair their replicative ability. This study provides evidence of the capacity of B-MYB not only to regulate p16 ( INK4α ) expression but also the phenotypic consequence on cellular senescence.
摘要
p16（INK4α）是细胞周期蛋白依赖性激酶 4 和 6 的抑制剂，它在细胞衰老和过早衰老中起着重要作用。p16（INK4α）的表达主要受转录控制。我们之前的数据表明，其启动子中存在一个负调控元件。在这个元件中，通过转录分析发现了一个 MYB 结合位点（MBS）。在这里，我们报告 MBS 是一个负调控元件，B-MYB 在体内结合到这个位点。在人胚肺成纤维细胞中，B-MYB 下调 p16（INK4α）的表达，而敲低 B-MYB 则上调其表达。有证据表明，细胞中 B-MYB 的过表达可以增加最高传代数并减少 G1 期阻滞，而敲低 B-MYB 则会损害其复制能力。这项研究提供了证据表明，B-MYB 不仅能够调节 p16（INK4α）的表达，还能对细胞衰老的表型后果产生影响。
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