ArticleProceedings of the National Academy of Sciences of the United States of America2000
Phosphorylation-dependent targeting of cAMP response element binding protein to the ubiquitin/proteasome pathway in hypoxia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 129 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
- The Role of Hyperbaric Oxygen Therapy in Neuroregeneration and Neuroprotection: A Review.Cureus · 2024Review
- The role of mitochondrial/metabolic axis in development of tamoxifen resistance in breast cancer.Human cell · 2023Review
- Recent Advances of Studies on Cell-Penetrating Peptides Based on Molecular Dynamics Simulations.Cells · 2022Review
- Muscarinic Acetylcholine Receptors-Mediated Activation of PKC Restores the Hippocampal Immediate Early Gene Expression and CREB Phosphorylation in Scopolamine-Induced Amnesic Mice.Molecular neurobiology · 2022Article
- Respiratory syncytial virus induces βScience signaling · 2021Article
- Down-Regulated CUEDC2 Increases GDNF Expression by Stabilizing CREB Through Reducing Its Ubiquitination in Glioma.Neurochemical research · 2020Article
- Methamphetamine induces cardiomyopathy by Sigmar1 inhibition-dependent impairment of mitochondrial dynamics and function.Communications biology · 2020Article
- What turns CREB on? And off? And why does it matter?Cellular and molecular life sciences : CMLS · 2020Review
- Review
- Proteasome limits plasticity-related signaling to the nucleus in the hippocampus.Neuroscience letters · 2018Article
- Highly polygenic architecture of antidepressant treatment response: Comparative analysis of SSRI and NRI treatment in an animal model of depression.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2017Article
- Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease.Blood advances · 2016Article
- Hypoxia-mediated alterations and their role in the HER-2/neuregulated CREB status and localization.Oncotarget · 2016Article
- Control of CREB expression in tumors: from molecular mechanisms and signal transduction pathways to therapeutic target.Oncotarget · 2016Review
- p21-activated kinase 4 critically regulates melanogenesis via activation of the CREB/MITF and β-catenin/MITF pathways.The Journal of investigative dermatology · 2015Article
- Differences in long-term memory stability and AmCREB level between forward and backward conditioned honeybees (Apis mellifera).Frontiers in behavioral neuroscience · 2015Article
- GSK3β controls epithelial-mesenchymal transition and tumor metastasis by CHIP-mediated degradation of Slug.Oncogene · 2014Article
- cAMP-response element-binding protein (CREB) and NF-κB transcription factors are activated during prolonged hypoxia and cooperatively regulate the induction of matrix metalloproteinase MMP1.The Journal of biological chemistry · 2013Article
- Role of cellular iron and oxygen in the regulation of HIV-1 infection.Future virology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia activates a number of gene products through degradation of the transcriptional coactivator cAMP response element binding protein (CREB). Other transcriptional regulators (e.g., beta-catenin and NF-kappa B) are controlled through phosphorylation-targeted proteasomal degradation, and thus, we hypothesized a similar degradative pathway for CREB. Differential display analysis of mRNA derived from hypoxic epithelia revealed a specific and time-dependent repression of protein phosphatase 1 (PP1), a serine phosphatase important in CREB dephosphorylation. Subsequent studies identified a previously unappreciated proteasomal-targeting motif within the primary structure of CREB (DSVTDS), which functions as a substrate for PP1. Ambient hypoxia resulted in temporally sequential CREB serine phosphorylation, ubiquitination, and degradation (in vitro and in vivo). HIV-tat peptide-facilitated loading of intact epithelia with phosphopeptides corresponding to this proteasome targeting motif resulted in inhibition of CREB ubiquitination. Further studies revealed that PP1 inhibitors mimicked hypoxia-induced gene expression, whereas proteasome inhibitors reversed the hypoxic phenotype. Thus, hypoxia establishes conditions that target CREB to proteasomal degradation. These studies may provide unique insight into a general mechanism of transcriptional regulation by hypoxia.
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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.