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Title 

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

Authors 

Haiyoung JungMi Jung KimDongoh KimWon Sam KimSung Jin YoonYoung-Jun ParkSuk Ran YoonTae-Don KimHyun Woo SuhSohyun YunJeong Ki MinHee Gu LeeY H LeeH J NaD C LeeHyoung-Chin KimIn Pyo Choi

Publisher 

Elsevier (Cell Press)

Issue Date 

2013

Citation 

Cell Metabolism, vol. 18, no. 1, pp. 75-85

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

Link 

http://dx.doi.org/10.1016/j.cmet.2013.06.002

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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