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B-MYB delays cell aging by repressing p16 INK4α transcription

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Abstract

p16INK4α, 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 p16INK4α 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 p16INK4α 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 p16INK4α expression but also the phenotypic consequence on cellular senescence.

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Acknowledgments

The authors are very grateful to Dr. Linda M. Boxer (Stanford University School of Medicine) for her kind gift of myb genes. We also thank Dr. Zhu Weiguo (Peking University Health Science Center) for important technological suggestions and supports.

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Authors and Affiliations

  1. Peking University Research Center on Aging, Peking University Health Science Center, 100083, Beijing, People’s Republic of China

    Yu Huang, Junfeng Wu, Renzhong Li, Peichang Wang, Limin Han, Zongyu Zhang & Tanjun Tong

  2. Department of Medical Genetics, Peking University Health Science Center, 100083, Beijing, People’s Republic of China

    Yu Huang

  3. Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 100083, Beijing, People’s Republic of China

    Junfeng Wu, Renzhong Li, Peichang Wang, Limin Han, Zongyu Zhang & Tanjun Tong

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  1. Yu Huang
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  2. Junfeng Wu
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  3. Renzhong Li
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  4. Peichang Wang
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  5. Limin Han
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  6. Zongyu Zhang
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  7. Tanjun Tong
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Corresponding author

Correspondence to Tanjun Tong.

Additional information

This work was supported by the grants from the National Basic Research Program of China (No. 2007CB507400) and the National Natural Science Foundation of China (No. 30800611).

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Huang, Y., Wu, J., Li, R. et al. B-MYB delays cell aging by repressing p16 INK4α transcription. Cell. Mol. Life Sci. 68, 893–901 (2011). https://doi.org/10.1007/s00018-010-0501-9

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  • DOI: https://doi.org/10.1007/s00018-010-0501-9

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