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Cited by 132Redox biology and oxidative stressHematopoietic Stem Cell TransplantationCancer-related Molecular Pathways

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

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Jung, Haiyoung, Kim, Mi Jeong, Kim, Dong Oh, Kim, Won Sam, Yoon, Sung-Jin, Park, Young-Jun, Yoon, Suk Ran, Kim, Tae-Don +9 more·2013·Cell Metabolism
DOI 10.1016/j.cmet.2013.06.002
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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.

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  • Txnip is a thiol-oxidoreductase that controls cellular redox signaling to protect cells from oxidative stress, and regulates hematopoietic stem cell quiescence under stress conditions by stabilizing p53 protein via direct interaction.

    “Txnip is a thiol-oxidoreductase that controls cellular redox signaling to protect cells from oxidative stress, and regulates HSC quiescence under stress conditions (34) by stabilizing p53 protein via direct interaction (38).”

    From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [38]

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Authors
Jung, H., Kim, M. J., Kim, D. O., Kim, W. S., Yoon, S.-J., Park, Y.-J., Yoon, S. R., Kim, T.-D., Suh, H.-W., Yun, S., Min, J.-K., Lee, H. G., Lee, Y. H., Na, H.-J., Lee, D. C., Kim, H.-C., & Choi, I.
Affiliations
  • Korea Research Institute of Bioscience and Biotechnology (KR)
  • Chungnam National University (KR)
Corresponding author
Choi, Inpyo
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2013-07
Volume
18
Issue
1
Pages
75-85
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2013.06.002
OpenAlex
W2056825486
Cited by
132
References
6
Citations by year
2026: 3 · 2025: 6 · 2024: 14 · 2023: 15 · 2022: 16 · 2021: 14 · 2020: 13 · 2019: 14 · 2018: 14 · 2017: 12 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 1
FWCI
1.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • KRIBB Repository (submittedVersion)
Funders
  • Ministry of Knowledge Economy
  • Ministry of Health and Welfare (DTM0241111)
  • Korea Research Institute of Bioscience and Biotechnology
  • Ministry of Education (A121934)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
TXNIP, p53, MDM2, reactive oxygen species, oxidative stress, hematopoietic stem cells, hematopoiesis, antioxidant genes, bone marrow, p53 transcriptional activity
MeSH terms
Animals, Antioxidants, Bone Marrow Cells, Carrier Proteins, Cells, Cultured, Hematopoiesis, Hematopoietic Stem Cells, Male, Mice, Inbred C57BL, Thioredoxins, Signal Transduction, Bone Marrow Transplantation, Tumor Suppressor Protein p53, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, Models, Animal, Mice, Proto-Oncogene Proteins c-mdm2

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