ArticleMolecular cell2025
SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging.
Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- SIRT7-Mediated H2BK120 Succinylation Drives Aberrant Mitophagy in Sepsis-Associated Cognitive Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibition of SIRT7 Overcomes Radioresistance in Pancreatic Neuroendocrine Tumors by Reactivating MEN1 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Sirtuin Network: Linking NADDiabetes/metabolism research and reviews · 2026Review
- TRIP12 promotes HIV-1 replication and latency reactivation by stabilizing Tat via USP7-mediated deubiquitination.Journal of virology · 2026Article
- SIRT7 safeguards ERα proteostasis via deacetylation-dependent degradation of unliganded and misfolded receptors.The Journal of biological chemistry · 2026Article
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- A Double-Edged Role for SIRT7 in Cancer: Can Anti-Cancer Immunity Tip the Balance?Pharmaceuticals (Basel, Switzerland) · 2025Review
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7 authors.
Funding
Abstract
Sirtuin enzymes are deeply associated with senescence and aging. Sirtuin proteins are tightly regulated, but how their levels are governed during aging and how they elicit tissue-specific cellular changes are unclear. Here, we demonstrate that SIRT7 undergoes proteasomal degradation during senescence via targeting by the E3 ligase TRIP12. We identified the transcription factor nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) as an interactor of SIRT7 and found NUCKS1 recruitment onto chromatin during senescence mediated by SIRT7 loss, correlating with increased NUCKS1 acetylation. NUCKS1 depletion delayed senescence, leading to reduced inflammatory gene expression associated with transcription factors RELA and CEBPβ. In Sirt7 knockout and aged mouse livers, NUCKS1 was bound at the promoters and enhancers of age-related genes, and these regulatory regions gained accessibility during aging. Overall, our results uncover NUCKS1 as an interactor of SIRT7 and indicate that proteasomal loss of SIRT7 during senescence and liver aging promotes NUCKS1 acetylation and chromatin binding to induce metabolic and inflammatory genes.
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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.