B-MYB delays cell aging by repressing p16 (INK4α) transcription.
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.
Huang
Yu
Y
Peking University Research Center on Aging, Peking University Health Science Center, Beijing, People's Republic of China.
Wu
Junfeng
J
Li
Renzhong
R
Wang
Peichang
P
Han
Limin
L
Zhang
Zongyu
Z
Tong
Tanjun
T
D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000502:physiology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D015536:Down-Regulation; D006801:Humans; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015534:Trans-Activators / Q000502:physiology*
D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; C064352:MYBL2 protein, human; D015534:Trans-Activators