ArticleCell death and differentiation2014
Role of Ku70 in deubiquitination of Mcl-1 and suppression of apoptosis.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
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- The Ku70-SIX1-GPT2 axis regulates alpha-ketoglutarate metabolism to drive progression of prostate cancer.Oncogene · 2025Article
- Unconventional activation of PRKDC by TNF-α: deciphering its crucial role in Th1-mediated inflammation beyond DNA repair as part of the DNA-PK complex.Journal of inflammation (London, England) · 2024Article
- Ubiquitin-proteasome pathway-mediated regulation of the Bcl-2 family: effects and therapeutic approaches.Haematologica · 2024Review
- ATR-dependent ubiquitin-specific protease 20 phosphorylation confers oxaliplatin and ferroptosis resistance.MedComm · 2023Article
- Targeting USP8 Inhibits O-GlcNAcylation of SLC7A11 to Promote Ferroptosis of Hepatocellular Carcinoma via Stabilization of OGT.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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- Mechanisms of MCL-1 Protein Stability Induced by MCL-1 Antagonists in B-Cell Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- The deubiquitinating enzyme MINDY2 promotes pancreatic cancer proliferation and metastasis by stabilizing ACTN4 expression and activating the PI3K/AKT/mTOR signaling pathway.Frontiers in oncology · 2023Article
- High-specificity protection against radiation-induced bone loss by a pulsed electromagnetic field.Science advances · 2022Article
- MCL-1 is a clinically targetable vulnerability in breast cancer.Cell cycle (Georgetown, Tex.) · 2022Review
- USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ.Cell death & disease · 2022Article
- Skp2 stabilizes Mcl-1 and confers radioresistance in colorectal cancer.Cell death & disease · 2022Article
- The regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer's disease.Acta materia medica · 2022Article
- Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it.Exploration of targeted anti-tumor therapy · 2022Review
- Gene expression and prognosis of x-ray repair cross-complementing family members in non-small cell lung cancer.Bioengineered · 2021Article
- RBMS1 regulates lung cancer ferroptosis through translational control of SLC7A11.The Journal of clinical investigation · 2021Article
- MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α.Cell death & disease · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Mcl-1 is a unique antiapoptotic Bcl2 family member with a short half-life due to its rapid turnover through ubiquitination. We discovered that Ku70, a DNA double-strand break repair protein, functions as a deubiquitinase to stabilize Mcl-1. Ku70 knockout in mouse embryonic fibroblast (MEF) cells or depletion from human lung cancer H1299 cells leads to the accumulation of polyubiquitinated Mcl-1 and a reduction in its half-life and protein expression. Conversely, expression of exogenous Ku70 in Ku70(-/-) MEF cells restores Mcl-1 expression. Subcellular fractionation indicates that Ku70 extensively colocalizes with Mcl-1 in mitochondria, endoplasmic reticulum and nucleus in H1299 cells. Ku70 directly interacts with Mcl-1 via its C terminus (that is, aa 536-609), which is required and sufficient for deubiquitination and stabilization of Mcl-1, leading to suppression of apoptosis. Purified Ku70 protein directly deubiquitinates Mcl-1 by removing K48-linked polyubiquitin chains. Ku70 knockdown not only promotes Mcl-1 turnover but also enhances antitumor efficacy of the BH3-mimetic ABT-737 in human lung cancer xenografts. These findings identify Ku70 as a novel Mcl-1 deubiquitinase that could be a potential target for cancer therapy by manipulating Mcl-1 deubiquitination.
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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.