ArticleNucleic acids research2016
Tunable regulation of CREB DNA binding activity couples genotoxic stress response and metabolism.
Article in Nucleic acids research, 2016. 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, 18 citations in OpenAlex.
- Targeted inhibition of the CREB1-CtIP axis enhances the efficacy of abiraterone combined with radiotherapy in prostate cancer.Cell death & disease · 2026Article
- Site-1 protease is a negative regulator of sarcolipin promoter activity.Communications biology · 2025Article
- AAV-Mediated Expression of miR-17 Enhances Neurite and Axon Regeneration In Vitro.International journal of molecular sciences · 2024Article
- Multi-faceted regulation of CREB family transcription factors.Frontiers in molecular neuroscience · 2024Review
- Glutamine-rich regions of the disordered CREB transactivation domain mediate dynamic intra- and intermolecular interactions.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Fused in sarcoma regulates DNA replication timing and kinetics.The Journal of biological chemistry · 2021Article
- IL-1β suppression of VE-cadherin transcription underlies sepsis-induced inflammatory lung injury.The Journal of clinical investigation · 2020Article
- Glucose Availability Alters Gene and Protein Expression of Several Newly Classified and Putative Solute Carriers in Mice Cortex Cell Culture andFrontiers in cell and developmental biology · 2020Article
- Increased mAb production in amplified CHO cell lines is associated with increased interaction of CREB1 with transgene promoter.Current research in biotechnology · 2019Article
- Sex-specific hepatic lipid and bile acid metabolism alterations inThe Journal of biological chemistry · 2019Article
- Structural Basis for Graded Inhibition of CREB:DNA Interactions by Multisite Phosphorylation.Biochemistry · 2018Article
- Linking CREB function with altered metabolism in murine fibroblast-based model cell lines.Oncotarget · 2017Article
- ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
cAMP response element binding protein (CREB) is a key regulator of glucose metabolism and synaptic plasticity that is canonically regulated through recruitment of transcriptional coactivators. Here we show that phosphorylation of CREB on a conserved cluster of Ser residues (the ATM/CK cluster) by the DNA damage-activated protein kinase ataxia-telangiectasia-mutated (ATM) and casein kinase1 (CK1) and casein kinase2 (CK2) positively and negatively regulates CREB-mediated transcription in a signal dependent manner. In response to genotoxic stress, phosphorylation of the ATM/CK cluster inhibited CREB-mediated gene expression, DNA binding activity and chromatin occupancy proportional to the number of modified Ser residues. Paradoxically, substoichiometric, ATM-independent, phosphorylation of the ATM/CK cluster potentiated bursts in CREB-mediated transcription by promoting recruitment of the CREB coactivator, cAMP-regulated transcriptional coactivators (CRTC2). Livers from mice expressing a non-phosphorylatable CREB allele failed to attenuate gluconeogenic genes in response to DNA damage or fully activate the same genes in response to glucagon. We propose that phosphorylation-dependent regulation of DNA binding activity evolved as a tunable mechanism to control CREB transcriptional output and promote metabolic homeostasis in response to rapidly changing environmental conditions.
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Registered trials
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