B-MYB delays cell aging by repressing p16 INK4α transcription
B-MYB delays cell aging by repressing p16 INK4α transcription
复制标题
DOI：
10.1007/s00018-010-0501-9
复制
发表时间：
2011-03-01
影响因子：
8
通讯作者：
Tong, Tanjun
中科院分区：
文献类型：
--
作者：
Huang, Yu;Wu, Junfeng;Tong, Tanjun
p16 （INK4 α）是细胞周期蛋白依赖性激酶4和6的抑制剂，在细胞衰老和过早衰老中起重要作用。p16 （INK4 α）的表达主要受转录控制。我们之前的数据表明，负调控元件存在于其启动子中。在该元件中，通过转录分析发现了myb结合位点（MBS）。在这里，我们报道了MBS是一个负调控元件，B-MYB在体内结合到这个位点。在人胚胎肺成纤维细胞中，B-MYB下调p16 （INK4 α）的表达，而B-MYB的下调上调p16 （INK4 α）的表达。有证据表明，B-MYB过表达可增加细胞的最大传代数，降低G1阻滞，而B-MYB过表达可损害细胞的复制能力。这项研究证明了B-MYB不仅能够调节p16 （INK4 α）的表达，而且还能对细胞衰老产生表型影响。
p16 (INK4 alpha) , 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 (INK4 alpha) 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 (INK4 alpha) 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 (INK4 alpha) expression but also the phenotypic consequence on cellular senescence.