ArticlePloS one2014
Cobalt and nickel stabilize stem cell transcription factor OCT4 through modulating its sumoylation and ubiquitination.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 40 citations in OpenAlex.
- Versatile roles of disordered transcription factor effector domains in transcriptional regulation.The FEBS journal · 2025Review
- An update on the effect of metals on stemness properties of mesenchymal stem cells.Journal of materials science. Materials in medicine · 2025Review
- OLMALINC/OCT4/BMP2 axis enhances osteogenic-like phenotype of renal interstitial fibroblasts to participate in Randall's plaque formation.Molecular medicine (Cambridge, Mass.) · 2022Article
- Protein sumoylation in normal and cancer stem cells.Frontiers in molecular biosciences · 2022Review
- Proteo-transcriptomics meta-analysis identifies SUMO2 as a promising target in glioblastoma multiforme therapeutics.Cancer cell international · 2021Article
- Assessing reference levels of nickel and chromium in cord blood, maternal blood and placenta specimens from Ankara, TurkeyJournal of the Turkish German Gynecological Association · 2021Article
- The FOXO signaling axis displays conjoined functions in redox homeostasis and stemness.Free radical biology & medicine · 2021Review
- Metal nickel exposure increase the risk of congenital heart defects occurrence in offspring: A case-control study in China.Medicine · 2019Article
- Intrauterine Exposure to Cadmium Reduces HIF-1 DNA-Binding Ability in Rat Fetal Kidneys.Toxics · 2018Article
- CD55 regulates self-renewal and cisplatin resistance in endometrioid tumors.The Journal of experimental medicine · 2017Article
- Cancer Stem-Like Cells Accumulated in Nickel-Induced Malignant Transformation.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Controlling Redox Status for Stem Cell Survival, Expansion, and Differentiation.Oxidative medicine and cellular longevity · 2015Review
- Toxicogenomic effect of nickel and beyond.Archives of toxicology · 2014Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Stem cell research can lead to the development of treatments for a wide range of ailments including diabetes, heart disease, aging, neurodegenerative diseases, spinal cord injury, and cancer. OCT4 is a master regulator of self-renewal of undifferentiated embryonic stem cells. OCT4 also plays a crucial role in reprogramming of somatic cells into induced pluripotent stem (iPS) cells. Given known vivo reproductive toxicity of cobalt and nickel metals, we examined the effect of these metals on expression of several stem cell factors in embryonic Tera-1 cells, as well as stem cells. Cobalt and nickel induced a concentration-dependent increase of OCT4 and HIF-1α, but not NANOG or KLF4. OCT4 induced by cobalt and nickel was due primarily to protein stabilization because MG132 stabilized OCT4 in cells treated with either metals and because neither nickel nor cobalt significantly modulated its steady-state mRNA level. OCT4 stabilization by cobalt and nickel was mediated largely through reactive oxygen species (ROS) as co-treatment with ascorbic acid abolished OCT4 increase. Moreover, nickel and cobalt treatment increased sumoylation and mono-ubiquitination of OCT4 and K123 was crucial for mediating these modifications. Combined, our observations suggest that nickel and cobalt may exert their reproductive toxicity through perturbing OCT4 activity in the stem cell compartment.
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Registered trials
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