Peking University Research Center on Aging, Peking University Health Science Center, Beijing, People's Republic of China.
Cell Mol Life Sci. 2011 Mar;68(5):893-901. doi: 10.1007/s00018-010-0501-9. Epub 2010 Aug 25.
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.
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。
