ArticleCell death and differentiation2016
HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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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Who cites it
46 citing papers in PubMed, 72 citations in OpenAlex.
- Identification of MKRN1 as a key modulator of the p53-MDM2 feedback loop.Cell death and differentiation · 2026Article
- Factors Determining Sirtuin-1 Target Engagement.Advanced biology · 2026Review
- A Dusty Affair: SIRT1-S682 Modulation Orchestrates ERK-FN1-p38-NF-κB Signaling and Composite-Dependent IL-8 Responses in Gingival Keratinocytes Exposed to Dental Dust and Eluates.Journal of functional biomaterials · 2026Article
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- A ZNF-nanobody fusion reveals SUMOylation-dependent changes in p53 protein localization.iScience · 2026Article
- Review
- Diffusion-based generation of gene regulatory networks from scRNA-seq data with DigNet.Genome research · 2025Article
- Crotonylation of MCM6 enhances chemotherapeutics sensitivity of breast cancer via inducing DNA replication stress.Cell proliferation · 2025Article
- Review
- A novel entity of HIPK2::YAP1 pulmonary fibromatosis.BMC pulmonary medicine · 2024Article
- Inhibitory protein-protein interactions of the SIRT1 deacetylase are choreographed by post-translational modification.Protein science : a publication of the Protein Society · 2024Article
- SIRT1 activated by AROS sensitizes glioma cells to ferroptosis via induction of NAD+ depletion-dependent activation of ATF3.Redox biology · 2024Article
- Article
- Insights into Regulators of p53 Acetylation.Cells · 2022Review
- Review
- Sirtuin1 in vascular endothelial function, an overview.Epigenetics · 2022Review
- The phosphorylation to acetylation/methylation cascade in transcriptional regulation: how kinases regulate transcriptional activities of DNA/histone-modifying enzymes.Cell & bioscience · 2022Review
- Targeting Mechanisms of the DNA Damage Response (DDR) and DNA Repair by Natural Compounds to Improve cAT-Triggered Tumor Cell Death.Molecules (Basel, Switzerland) · 2022Article
- The miRNA-34a/Sirt1/p53 pathway in a rat model of lens regeneration.Annals of translational medicine · 2022Article
- JNK-mediated Ser27 phosphorylation and stabilization of SIRT1 promote growth and progression of colon cancer through deacetylation-dependent activation of Snail.Molecular oncology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon severe DNA damage a cellular signalling network initiates a cell death response through activating tumour suppressor p53 in association with promyelocytic leukaemia (PML) nuclear bodies. The deacetylase Sirtuin 1 (SIRT1) suppresses cell death after DNA damage by antagonizing p53 acetylation. To facilitate efficient p53 acetylation, SIRT1 function needs to be restricted. How SIRT1 activity is regulated under these conditions remains largely unclear. Here we provide evidence that SIRT1 activity is limited upon severe DNA damage through phosphorylation by the DNA damage-responsive kinase HIPK2. We found that DNA damage provokes interaction of SIRT1 and HIPK2, which phosphorylates SIRT1 at Serine 682 upon lethal damage. Furthermore, upon DNA damage SIRT1 and HIPK2 colocalize at PML nuclear bodies, and PML depletion abrogates DNA damage-induced SIRT1 Ser682 phosphorylation. We show that Ser682 phosphorylation inhibits SIRT1 activity and impacts on p53 acetylation, apoptotic p53 target gene expression and cell death. Mechanistically, we found that DNA damage-induced SIRT1 Ser682 phosphorylation provokes disruption of the complex between SIRT1 and its activator AROS. Our findings indicate that phosphorylation-dependent restriction of SIRT1 activity by HIPK2 shapes the p53 response.
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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.