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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Version of Record online: 24 JUL 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 8, pages 1634–1644, August 2012
How to Cite
Hishida, T., Nozaki, Y., Nakachi, Y., Mizuno, Y., Iseki, H., Katano, M., Kamon, M., Hirasaki, M., Nishimoto, M., Okazaki, Y. and Okuda, A. (2012), Sirt1, p53, and p38MAPK Are Crucial Regulators of Detrimental Phenotypes of Embryonic Stem Cells with Max Expression Ablation. STEM CELLS, 30: 1634–1644. doi: 10.1002/stem.1147
Author contributions: T.H.: conception and design, data analysis and interpretation, and manuscript writing; Y. Nozaki, Y. Nakachi, Y.M., H.I., M. Katano, M. Kamon, M.H., M.N., and Y.O.: data analysis and interpretation; A.O.: conception and design, financial support, and manuscript writing.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS June 13, 2012.
- Issue online: 24 JUL 2012
- Version of Record online: 24 JUL 2012
- Accepted manuscript online: 13 JUN 2012 02:37PM EST
- Manuscript Accepted: 31 MAY 2012
- Manuscript Received: 29 FEB 2012
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan
- Strategic Research Center in Private Universities to the Saitama Medical University Research Center for Genomic Medicine
- Embryonic stem cells;
c-Myc participates in diverse cellular processes including cell cycle control, tumorigenic transformation, and reprogramming of somatic cells to induced pluripotent cells. c-Myc is also an important regulator of self-renewal and pluripotency of embryonic stem cells (ESCs). We recently demonstrated that loss of the Max gene, encoding the best characterized partner for all Myc family proteins, causes loss of the pluripotent state and extensive cell death in ESCs strictly in this order. However, the mechanisms and molecules that are responsible for these phenotypes remain largely obscure. Here, we show that Sirt1, p53, and p38MAPK are crucially involved in the detrimental phenotype of Max-null ESCs. Moreover, our analyses revealed that these proteins are involved at varying levels to one another in the hierarchy of the pathway leading to cell death in Max-null ESCs. STEM CELLS2012;30:1634–1644