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

Cell Metab. 2013 Jul 2;18(1):75-85. doi: 10.1016/j.cmet.2013.06.002.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / physiology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology
  • Bone Marrow Transplantation
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cells, Cultured
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Oxidative Stress / physiology*
  • Proto-Oncogene Proteins c-mdm2 / physiology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology*
  • Thioredoxins / genetics
  • Thioredoxins / physiology*
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology*


  • Antioxidants
  • Carrier Proteins
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • Txnip protein, mouse
  • Thioredoxins
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2