ArticleMolecular biology of the cell2012
Multilevel regulation of HIF-1 signaling by TTP.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Review
- Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway.bioRxiv : the preprint server for biology · 2023Article
- Identification ofMolecules (Basel, Switzerland) · 2022Article
- Cottonseed extracts regulate gene expression in human colon cancer cells.Scientific reports · 2022Article
- PAQR11 modulates monocyte-to-macrophage differentiation and pathogenesis of rheumatoid arthritis.Immunology · 2021Article
- Gossypol decreased cell viability and down-regulated the expression of a number of genes in human colon cancer cells.Scientific reports · 2021Article
- ARE-mediated decay controls gene expression and cellular metabolism upon oxygen variations.Scientific reports · 2018Article
- Post-transcriptional regulation of cytokine and growth factor signaling in cancer.Cytokine & growth factor reviews · 2017Review
- Dysregulation of TTP and HuR plays an important role in cancers.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Tristetraprolin induces cell cycle arrest in breast tumor cells through targeting AP-1/c-Jun and NF-κB pathway.Oncotarget · 2015Article
- AML1/ETO cooperates with HIF1α to promote leukemogenesis through DNMT3a transactivation.Leukemia · 2015Article
- Inactivation of tristetraprolin in chronic hypoxia provokes the expression of cathepsin B.Molecular and cellular biology · 2015Article
- Differential expression of transcription factors and inflammation-, ROS-, and cell death-related genes in organotypic cultures in the modiolus, the organ of Corti and the stria vascularis of newborn rats.Cellular and molecular neurobiology · 2014Article
- MicroRNA-let-7a expression is increased in the mesangial cells of NZB/W mice and increases IL-6 production in vitro.Autoimmunity · 2013Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor-1 (HIF-1) is a well-studied transcription factor mediating cellular adaptation to hypoxia. It also plays a crucial role under normoxic conditions, such as in inflammation, where its regulation is less well understood. The 3'-untranslated region (UTR) of HIF-1α mRNA is among the most conserved UTRs in the genome, hinting toward posttranscriptional regulation. To identify potential trans factors, we analyzed a large compilation of expression data. In contrast to its known function of being a negative regulator, we found that tristetraprolin (TTP) positively correlates with HIF-1 target genes. Mathematical modeling predicts that an additional level of posttranslational regulation of TTP can explain the observed positive correlation between TTP and HIF-1 signaling. Mechanistic studies revealed that TTP indeed changes its mode of regulation from destabilizing to stabilizing HIF-1α mRNA upon phosphorylation by p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein kinase 2. Using a model of monocyte-to-macrophage differentiation, we show that TTP-driven HIF-1α mRNA stabilization is crucial for cell migration. This demonstrates the physiological importance of a hitherto-unknown mechanism for multilevel regulation of HIF-1α in normoxia.
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