ArticleProceedings of the National Academy of Sciences of the United States of America2003
Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
84 citing papers in PubMed, 183 citations in OpenAlex.
- A plasma derived hypoxia signature predicts benefit from hypoxia-modifying radiotherapy and reveals dynamic humoral immune modulation in bladder cancer.British journal of cancer · 2026Article
- Article
- Hypoxia, ROS, and HIF Signaling in I/R Injury: Implications and Future Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Distinctive tumorigenic significance and innovative oncology targets of SUMOylation.Theranostics · 2024Review
- Multi-faceted regulation of CREB family transcription factors.Frontiers in molecular neuroscience · 2024Review
- Oxygen-regulated post-translation modifications as master signalling pathway in cells.EMBO reports · 2023Review
- The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications.Experimental hematology & oncology · 2023Review
- Therapeutic Effects and Molecular Mechanism of Chlorogenic Acid on Polycystic Ovarian Syndrome: Role of HIF-1alpha.Nutrients · 2023Review
- The effect of HIF on metabolism and immunity.Nature reviews. Nephrology · 2022Review
- The disruption of the CCDC6 - PP4 axis induces a BRCAness like phenotype and sensitivity to PARP inhibitors in high-grade serous ovarian carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Conserved E1B-55K SUMOylation in Different Human Adenovirus Species Is a Potent Regulator of Intracellular Localization.Journal of virology · 2022Article
- Natural Products Against Renal FibrosisFrontiers in pharmacology · 2022Review
- CREB1ACS omega · 2021Article
- Review
- Sumoylation of the Carboxy-Terminal of Human Cytomegalovirus DNA Polymerase Processivity Factor UL44 Attenuates Viral DNA Replication.Frontiers in microbiology · 2021Article
- High Migration and Invasion Ability of PGCCs and Their Daughter Cells Associated With the Nuclear Localization of S100A10 Modified by SUMOylation.Frontiers in cell and developmental biology · 2021Article
- In Situ DNA/Protein Interaction Assay to Visualize Transcriptional Factor Activation.Methods and protocols · 2020Article
- Review
- Review
- What turns CREB on? And off? And why does it matter?Cellular and molecular life sciences : CMLS · 2020Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Phosphorylation-dependent ubiquitination combined with proteasomal degradation of transcriptional regulators is a recently appreciated mechanism for control of a number of inflammatory genes. Far less is known about the counterregulatory mechanisms that repress transcriptional activity in these pathways during resolution. Here, we investigated the transient nature of hypoxia-induced tumor necrosis factor (TNF)alpha in T84 cells, a process we have previously shown to involve phosphorylation-dependent degradation of the cAMP-response element-binding protein (CREB). Initial studies indicate hypoxia-induced TNFalpha to be a transient event, the resolution of which is associated with the appearance of a higher molecular weight modified form of CREB. Gene array analysis of mRNA derived from hypoxic cells identified a time-dependent induction of small ubiquitin-related modifier (SUMO)-1 mRNA. In prolonged hypoxia, CREB is posttranslationally modified by SUMO-1. Furthermore, SUMO-1 overexpression stabilizes CREB in hypoxia and enhances CREB-dependent reporter gene activity. Site-directed mutagenesis of lysine residues K285 and K304 identifies them as SUMO acceptors in vivo and in vitro. Mutation of K304 also results in loss of CREB nuclear localization, implying a role for SUMO-1 modification at this site in the subcellular localization of CREB. Thus, in prolonged hypoxia, CREB is modified by association with SUMO-1. Furthermore, we hypothesize that such an event stabilizes and promotes nuclear localization of CREB and thus complements an endogenous resolution phase for hypoxia-induced inflammatory processes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.