ArticleCell death and differentiation2012
Identification of an acetylation-dependant Ku70/FLIP complex that regulates FLIP expression and HDAC inhibitor-induced apoptosis.
Article in Cell death and differentiation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 106 citations in OpenAlex.
- CK2-mediated HDAC5 shuttling regulates DNA end resection through Ku70 deacetylation.Theranostics · 2026Article
- Epigenetic marvels: exploring the landscape of colorectal cancer treatment through cutting-edge epigenetic-based drug strategies.Clinical epigenetics · 2025Review
- WT161, a selective HDAC6 inhibitor, decreases growth, enhances chemosensitivity, promotes apoptosis, and suppresses motility of melanoma cells.Cancer chemotherapy and pharmacology · 2025Article
- Identification of biomarkers for the diagnosis of chronic kidney disease (CKD) with dilated cardiomyopathy (DCM) by bioinformatics analysis and machine learning.Frontiers in genetics · 2025Article
- EX527, a sirtuins 1 inhibitor, sensitizes T-cell leukemia to death receptor-mediated apoptosis by downregulating cellular FLICE inhibitory protein.Cancer biology & therapy · 2024Article
- Cellular Dynamics of Fas-Associated Death Domain in the Regulation of Cancer and Inflammation.International journal of molecular sciences · 2024Review
- Role of Histone Deacetylase 6 and Histone Deacetylase 6 Inhibition in Colorectal Cancer.Pharmaceutics · 2023Review
- UBE4B interacts with the ITCH E3 ubiquitin ligase to induce Ku70 and c-FLIPL polyubiquitination and enhanced neuroblastoma apoptosis.Cell death & disease · 2023Article
- (-)-Epigallocatechin-3-gallate induced apoptosis by dissociation of c-FLIP/Ku70 complex in gastric cancer cells.Journal of cellular and molecular medicine · 2023Article
- Acetylation of the nuclear localization signal in Ku70 diminishes the interaction with importin-α.Biochemistry and biophysics reports · 2023Article
- Rational design of metabolically stable HDAC inhibitors: An overhaul of trifluoromethyl ketones.European journal of medicinal chemistry · 2022Article
- HDAC6: A unique HDAC family member as a cancer target.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Article
- Restoring TRAILR2/DR5-Mediated Activation of Apoptosis upon Endoplasmic Reticulum Stress as a Therapeutic Strategy in Cancer.International journal of molecular sciences · 2022Review
- The deubiquitinase Usp27x as a novel regulator of cFLIPApoptosis : an international journal on programmed cell death · 2022Article
- Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer.Molecular cancer therapeutics · 2021Article
- Article
- Role of HDAC6 and Its Selective Inhibitors in Gastrointestinal Cancer.Frontiers in cell and developmental biology · 2021Review
- The pseudo-caspase FLIP(L) regulates cell fate following p53 activation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- SIRT1 Deficiency, Specifically in Fibroblasts, Decreases Apoptosis Resistance and Is Associated with Resolution of Lung-Fibrosis.Biomolecules · 2020Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
FLIP is a potential anti-cancer therapeutic target that inhibits apoptosis by blocking caspase 8 activation by death receptors. We report a novel interaction between FLIP and the DNA repair protein Ku70 that regulates FLIP protein stability by inhibiting its polyubiquitination. Furthermore, we found that the histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) enhances the acetylation of Ku70, thereby disrupting the FLIP/Ku70 complex and triggering FLIP polyubiquitination and degradation by the proteasome. Using in vitro and in vivo colorectal cancer models, we further demonstrated that SAHA-induced apoptosis is dependant on FLIP downregulation and caspase 8 activation. In addition, an HDAC6-specific inhibitor Tubacin recapitulated the effects of SAHA, suggesting that HDAC6 is a key regulator of Ku70 acetylation and FLIP protein stability. Thus, HDAC inhibitors with anti-HDAC6 activity act as efficient post-transcriptional suppressors of FLIP expression and may, therefore, effectively act as 'FLIP inhibitors'.
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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.