TXNIP maintains the hematopoietic cell pool by switching the function of p53 under oxidative stress

Cited 78 time in scopus
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Title
TXNIP maintains the hematopoietic cell pool by switching the function of p53 under oxidative stress
Author(s)
Haiyoung Jung; Mi Jung Kim; Dongoh Kim; Won Sam Kim; Sung Jin YoonYoung-Jun ParkSuk Ran YoonTae-Don Kim; Hyun Woo Suh; Sohyun Yun; Jeong Ki Min; Hee Gu Lee; Y H Lee; H J Na; Dong Chul LeeHyoung-Chin Kim; In Pyo Choi
Bibliographic Citation
Cell Metabolism, vol. 18, no. 1, pp. 75-85
Publication Year
2013
Abstract
Reactive oxygen species (ROS) are critical determinants of the fate of hematopoietic stem cells (HSCs) and hematopoiesis. Thioredoxin-interacting protein (TXNIP), which is induced by oxidative stress, is a known regulator of intracellular ROS. Txnip-/- old mice exhibited elevated ROS levels in hematopoietic cells and showed a reduction in hematopoietic cell population. Loss of TXNIP led to a dramatic reduction of mouse survival under oxidative stress. TXNIP directly regulated p53 protein by interfering with p53- mouse double minute 2 (MDM2) interactions and increasing p53 transcriptional activity. Txnip-/- mice showed downregulation of the antioxidant genes induced by p53. Introduction of TXNIP or p53 into Txnip-/- bone marrow cells rescued the HSC frequency and greatly increased survival in mice following oxidative stress. Overall, these data indicate that TXNIP is a regulator of p53 and plays a pivotal role in the maintenance of the hematopoietic cells by regulating intracellular ROS during oxidative stress
ISSN
1550-4131
Publisher
Elsevier-Cell Press
DOI
http://dx.doi.org/10.1016/j.cmet.2013.06.002
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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