ArticleNucleic acids research2017
SIRT6 interacts with TRF2 and promotes its degradation in response to DNA damage.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 63 citations in OpenAlex.
- Evaluation of Molecular Responses and Longevity Markers inInternational journal of molecular sciences · 2026Article
- Telomeres control human telomerase (eLife · 2025Article
- Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development.Current oncology (Toronto, Ont.) · 2025Review
- miR-23a-mediated TRF2 repression in CD4 T cells from PLWH.Molecular immunology · 2025Article
- TRF2 interaction with nuclear envelope is required for cell polarization and metastasis in triple negative breast cancer.Cell death & disease · 2025Article
- Article
- The telomeric protein TERF2/TRF2 impairs HMGB1-driven autophagy.Autophagy · 2023Article
- PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment.Communications biology · 2023Article
- Review
- Telomere Status of Advanced Non-Small-Cell Lung Cancer Offers a Novel Promising Prognostic and Predictive Biomarker.Cancers · 2022Article
- SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases.Aging and disease · 2022Review
- The role of epigenetic modifications in Colorectal Cancer Metastasis.Clinical & experimental metastasis · 2022Review
- TRF2 inhibition rather than telomerase disruption drives CD4T cell dysfunction during chronic viral infection.Journal of cell science · 2022Article
- Telomere Targeting Approaches in Cancer: Beyond Length Maintenance.International journal of molecular sciences · 2022Review
- Sirtuin 6 Is a Critical Epigenetic Regulator of Cancer.Sub-cellular biochemistry · 2022Review
- Roles of SIRT6 in kidney disease: a novel therapeutic target.Cellular and molecular life sciences : CMLS · 2021Article
- Sirtuin 6: linking longevity with genome and epigenome stability.Trends in cell biology · 2021Review
- Emerging Therapeutic Potential of SIRT6 Modulators.Journal of medicinal chemistry · 2021Review
- The Two-Faced Role of SIRT6 in Cancer.Cancers · 2021Review
- A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injuryActa pharmaceutica Sinica. B · 2021Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Telomere repeat binding factor 2 (TRF2) has been increasingly recognized to be involved in telomere maintenance and DNA damage response. Here, we show that TRF2 directly binds SIRT6 in a DNA independent manner and that this interaction is increased upon replication stress. Knockdown of SIRT6 up-regulates TRF2 protein levels and counteracts its down-regulation during DNA damage response, leading to cell survival. Moreover, we report that SIRT6 deactetylates in vivo the TRFH domain of TRF2, which in turn, is ubiquitylated in vivo activating the ubiquitin-dependent proteolysis. Notably, overexpression of the TRF2cT mutant failed to be stabilized by SIRT6 depletion, demonstrating that the TRFH domain is required for its post-transcriptional modification. Finally, we report an inverse correlation between SIRT6 and TRF2 protein expression levels in a cohort of colon rectal cancer patients. Taken together our findings describe TRF2 as a novel SIRT6 substrate and demonstrate that acetylation of TRF2 plays a crucial role in the regulation of TRF2 protein stability, thus providing a new route for modulating its expression level during oncogenesis and damage 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.