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Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells

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2008
190.pdf (3.048Mb)
Authors
Yalcin, Safak
Zhang, Xin
Luciano, Julia P.
Mungamuri, Sathish Kumar
Marinković, Dragan
Vercherat, Cecile
Sarkar, Abby
Grisotto, Marcos
Taneja, Reshma
Ghaffari, Saghi
Article (Published version)
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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 p16(INK4a) and ROS-mediated activation of p53/p21(CIP1/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 maintenanc...e of the hematopoietic stem cell pool.

Source:
Journal of Biological Chemistry, 2008, 283, 37, 25692-25705
Publisher:
  • Amer Soc Biochemistry Molecular Biology Inc, Bethesda
Funding / projects:
  • American Cancer Society Research Scholarship [RSG LIB-110480]
  • Career Enhancement Award [K18 HL76510-01]
  • Black Family Stem Cell Institute
  • Mount Sinai School of Medicine research funds

DOI: 10.1074/jbc.M800517200

ISSN: 0021-9258

PubMed: 18424439

WoS: 000259012700064

Scopus: 2-s2.0-54449092731
[ Google Scholar ]
204
180
URI
http://rfasper.fasper.bg.ac.rs/handle/123456789/193
Collections
  • Radovi istraživača / Researcher's publications
Institution/Community
rFASPER
TY  - JOUR
AU  - Yalcin, Safak
AU  - Zhang, Xin
AU  - Luciano, Julia P.
AU  - Mungamuri, Sathish Kumar
AU  - Marinković, Dragan
AU  - Vercherat, Cecile
AU  - Sarkar, Abby
AU  - Grisotto, Marcos
AU  - Taneja, Reshma
AU  - Ghaffari, Saghi
PY  - 2008
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/193
AB  - 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 p16(INK4a) and ROS-mediated activation of p53/p21(CIP1/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.
PB  - Amer Soc Biochemistry Molecular Biology Inc, Bethesda
T2  - Journal of Biological Chemistry
T1  - Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells
EP  - 25705
IS  - 37
SP  - 25692
VL  - 283
DO  - 10.1074/jbc.M800517200
ER  - 
@article{
author = "Yalcin, Safak and Zhang, Xin and Luciano, Julia P. and Mungamuri, Sathish Kumar and Marinković, Dragan and Vercherat, Cecile and Sarkar, Abby and Grisotto, Marcos and Taneja, Reshma and Ghaffari, Saghi",
year = "2008",
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 p16(INK4a) and ROS-mediated activation of p53/p21(CIP1/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.",
publisher = "Amer Soc Biochemistry Molecular Biology Inc, Bethesda",
journal = "Journal of Biological Chemistry",
title = "Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells",
pages = "25705-25692",
number = "37",
volume = "283",
doi = "10.1074/jbc.M800517200"
}
Yalcin, S., Zhang, X., Luciano, J. P., Mungamuri, S. K., Marinković, D., Vercherat, C., Sarkar, A., Grisotto, M., Taneja, R.,& Ghaffari, S.. (2008). Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells. in Journal of Biological Chemistry
Amer Soc Biochemistry Molecular Biology Inc, Bethesda., 283(37), 25692-25705.
https://doi.org/10.1074/jbc.M800517200
Yalcin S, Zhang X, Luciano JP, Mungamuri SK, Marinković D, Vercherat C, Sarkar A, Grisotto M, Taneja R, Ghaffari S. Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells. in Journal of Biological Chemistry. 2008;283(37):25692-25705.
doi:10.1074/jbc.M800517200 .
Yalcin, Safak, Zhang, Xin, Luciano, Julia P., Mungamuri, Sathish Kumar, Marinković, Dragan, Vercherat, Cecile, Sarkar, Abby, Grisotto, Marcos, Taneja, Reshma, Ghaffari, Saghi, "Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells" in Journal of Biological Chemistry, 283, no. 37 (2008):25692-25705,
https://doi.org/10.1074/jbc.M800517200 . .

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