Please use this identifier to cite or link to this item: https://doi.org/10.1074/jbc.M800517200
Title: Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells
Authors: Yalcin, S.
Zhang, X.
Luciano, J.P.
Mungamuri, S.K.
Marinkovic, D.
Vercherat, C.
Sarkar, A.
Grisotto, M.
Taneja, R. 
Ghaffari, S.
Issue Date: 12-Sep-2008
Citation: Yalcin, S., Zhang, X., Luciano, J.P., Mungamuri, S.K., Marinkovic, D., Vercherat, C., Sarkar, A., Grisotto, M., Taneja, R., Ghaffari, S. (2008-09-12). Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells. Journal of Biological Chemistry 283 (37) : 25692-25705. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M800517200
Abstract: Unchecked accumulation of reactive oxygen species (ROS) compromises maintenance of hematopoietic stem cells. Regulation of ROS by the tumor suppressor protein ataxia telangiectasia mutated (ATM) is critical for preserving the hematopoietic stem cell pool. In this study we demonstrate that the Foxo3 member of the Forkhead Box O (FoxO) family of transcription factors is essential for normal ATM expression. In addition, we show that loss of Foxo3 leads to defects in hematopoietic stem cells, and these defects result from an overaccumulation of ROS. Foxo3 suppression of ROS in hematopoietic stem cells is mediated partly by regulation of ATM expression. We identify ROS-independent modulations of ATM and p16INK4a and ROS-mediated activation of p53/p21CIP1/WAF1/Sdi1 tumor suppressor pathways as major contributors to Foxo3-null hematopoietic stem cells defects. Our studies demonstrate that Foxo3 represses ROS in part via regulation of ATM and that this repression is required for maintenance of the hematopoietic stem cell pool. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/132836
ISSN: 00219258
DOI: 10.1074/jbc.M800517200
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