Current address: Department of Pathology, University of California, San Francisco, CA 94143, USA.
SnoN activates p53 directly to regulate aging and tumorigenesis
Article first published online: 27 AUG 2012
© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland
Volume 11, Issue 5, pages 902–911, October 2012
How to Cite
Pan, D., Zhu, Q., Conboy, M. J., Conboy, I. M. and Luo, K. (2012), SnoN activates p53 directly to regulate aging and tumorigenesis. Aging Cell, 11: 902–911. doi: 10.1111/j.1474-9726.2012.00857.x
- Issue published online: 16 SEP 2012
- Article first published online: 27 AUG 2012
- Accepted manuscript online: 16 JUL 2012 12:40PM EST
- Accepted for publication 5 July 2012
- accelerated aging;
- mouse models;
We have identified SnoN as a direct activator of p53 to accelerate aging and inhibit tumorigenesis. SnoN has been shown previously to promote proliferation and transformation by antagonizing TGFβ signaling. We show that elimination of this TGFβ antagonistic activity of SnoN in vivo results in accelerated aging and resistance to tumorigenesis. The SnoN knockin mice display a shortened lifespan, decreased reproductivity, osteoporosis, reduced regenerative capacity, and other aging phenotypes, similar to that found in mice expressing an active p53. These activities of SnoN rely on the ability of SnoN to activate p53. SnoN can bind directly to p53 and compete with Mdm2 for binding to p53, preventing p53 ubiquitination and degradation and additionally facilitating p53 acetylation and phosphorylation. SnoN also binds to p53 on the promoter of p53 responsive genes to promote transcription activation. This activation of p53 by SnoN is necessary for its antitumorigenic and progeria activities in vivo because elimination of one copy of p53 reverses the aging phenotypes and accelerates tumorigenesis. Thus, we have revealed a novel function of SnoN in regulating aging and tumorigenesis by directly activating p53.