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

The Journal of Biological Chemistry
Safak YalcinSaghi Ghaffari

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.

References

Jul 12, 1996·Cell·C BarlowA Wynshaw-Boris
Apr 30, 1998·Physiological Reviews·K B Beckman, B N Ames
Mar 10, 2000·Science·T ChengD T Scadden
Nov 1, 2001·Annual Review of Cell and Developmental Biology·I L WeissmanF Gage
Jan 5, 2002·Physiological Reviews·Wulf Dröge
Sep 20, 2002·Nature·Geert J P L KopsBoudewijn M T Burgering
Jan 31, 2003·Nature·Christopher J Bakkenist, Michael B Kastan
May 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Saghi GhaffariRoya Khosravi-Far
Jul 12, 2003·Science·Diego H CastrillonRonald A DePinho
Jan 28, 2004·Cell·Charles J Sherr
Sep 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Han YouTak W Mak
Nov 13, 2004·The EMBO Journal·Marieke A G EssersBoudewijn M T Burgering
Dec 22, 2004·Cell Cycle·Han You, Tak W Mak
Dec 7, 2005·The Journal of Experimental Medicine·Emmanuelle PasseguéIrving L Weissman
Jun 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Han YouTak Wah Mak
Aug 3, 2007·The Journal of Clinical Investigation·Dragan MarinkovicSaghi Ghaffari
Mar 18, 2008·Nature Cell Biology·Wen-Bin TsaiMickey C-T Hu
Mar 29, 2008·Cell Stem Cell·Kana MiyamotoAtsushi Hirao
Mar 1, 1993·Journal of Microscopy·E M M MandersJ A Aten

❮ Previous
Next ❯

Citations

Mar 9, 2011·International Journal of Hematology·Kazuhito Naka, Atsushi Hirao
May 14, 2011·International Journal of Hematology·Lijian ShaoDaohong Zhou
Jun 15, 2011·International Journal of Hematology·Zhenyu JuTao Cheng
Mar 16, 2013·Cell Death & Disease·Kui WangYuquan Wei
Sep 27, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Anthony D D'SouzaGerald S Shadel
Aug 2, 2011·Nature Cell Biology·Xin ZhangSaghi Ghaffari
Aug 16, 2012·Nature Communications·Young Min ChungMickey C-T Hu
Aug 25, 2009·Nature Immunology·Stephen M Hedrick
Sep 11, 2012·Nature Medicine·Hal E Broxmeyer, Charlie Mantel
Nov 30, 2013·Nature Reviews. Drug Discovery·Chiara GorriniTak W Mak
Aug 25, 2012·Nature Reviews. Immunology·Stephen M HedrickErica L Stone
Feb 10, 2011·Nature Reviews. Molecular Cell Biology·Pankaj K MandalDerrick J Rossi
Jan 18, 2013·Nature Reviews. Molecular Cell Biology·Astrid Eijkelenboom, Boudewijn M T Burgering
Oct 16, 2013·The Journal of Cell Biology·Joshua D Ochocki, M Celeste Simon
Aug 19, 2008·Antioxidants & Redox Signaling·Saghi Ghaffari
Aug 5, 2009·Antioxidants & Redox Signaling·Shazib PervaizSaghi Ghaffari
Jul 14, 2010·Antioxidants & Redox Signaling·Peter Storz
Jul 14, 2010·Antioxidants & Redox Signaling·Maaike C W van den Berg, Boudewijn M T Burgering
Sep 18, 2012·Antioxidants & Redox Signaling·Paraskevi Charitou, Boudewijn M T Burgering
Apr 12, 2012·Molecular Biology of the Cell·Kathrin GeigerPetra Obexer
Aug 15, 2009·Human Molecular Genetics·Cécile VercheratReshma Taneja
Oct 7, 2011·Journal of Signal Transduction·Hang CuiHong Zhang
Feb 20, 2013·Journal of Cell Science·Victoria A RafalskiAnne Brunet
May 3, 2013·PLoS Computational Biology·Hans B SieburgChrista E Muller-Sieburg
Jul 30, 2010·PloS One·Luca GoitreSaverio Francesco Retta
Jan 5, 2014·Antioxidants & Redox Signaling·Raymond Liang, Saghi Ghaffari
Oct 8, 2013·Trends in Cell Biology·David VilchezAndrew Dillin
Oct 17, 2012·Antioxidants & Redox Signaling·Pooja ChaudhariYoon-Young Jang
Oct 16, 2013·Antioxidants & Redox Signaling·Lijian ShaoDaohong Zhou
Apr 30, 2013·Antioxidants & Redox Signaling·Cheng Cheng Zhang, Hesham A Sadek
Jul 8, 2014·Antioxidants & Redox Signaling·Wataru KimuraHesham A Sadek
Aug 8, 2014·Nature Medicine·Juhyun OhAmy J Wagers
Jun 18, 2014·The Journal of Clinical Investigation·Brian S Garrison, Derrick J Rossi
Mar 7, 2014·Antioxidants & Redox Signaling·Polina GoichbergAnnarosa Leri
Oct 4, 2014·Trends in Molecular Medicine·Nadine MartinJesús Gil
Dec 24, 2009·Canadian Journal of Physiology and Pharmacology·Istvan LekliDipak K Das
Jun 13, 2009·Cell Transplantation·Xiaosong HuangGerald J Spangrude
May 3, 2011·Cellular and Molecular Life Sciences : CMLS·Shahzad BhattiKum Kum Khanna
Mar 27, 2009·Neurochemical Research·Wenqiang ChenMohammed A Junaid

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.