ArticleGenes & development2011
Mule determines the apoptotic response to HDAC inhibitors by targeted ubiquitination and destruction of HDAC2.
Article in Genes & development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
The trial behind it
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- HUWE1 in Skeletal Muscle Prevents Muscle Fatigue via Maintaining Iron and Calcium Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- Sox2 interacts with Atoh1 and Huwe1 loci to regulate Atoh1 transcription and stability during hair cell differentiation.PLoS genetics · 2025Article
- Ubiquitin ligase E3 HUWE1/MULE targets transferrin receptor for degradation and suppresses ferroptosis in acute liver injury.Cell death and differentiation · 2022Article
- The E3 ubiquitin ligase HUWE1 acts through the N-Myc-DLL1-NOTCH1 signaling axis to suppress glioblastoma progression.Cancer communications (London, England) · 2022Article
- The giant E3 ligase HUWE1 is linked to tumorigenesis, spermatogenesis, intellectual disability, and inflammatory diseases.Frontiers in cellular and infection microbiology · 2022Review
- Proteasomal Degradation of Zn-Dependent Hdacs: The E3-Ligases Implicated and the Designed Protacs That Enable Degradation.Molecules (Basel, Switzerland) · 2021Review
- Review
- Chidamide combined with paclitaxel effectively reverses the expression of histone deacetylase in lung cancer.Anti-cancer drugs · 2020Article
- The structure and regulation of the E3 ubiquitin ligase HUWE1 and its biological functions in cancer.Investigational new drugs · 2020Review
- Ubiquitin specific peptidase 5 promotes ovarian cancer cell proliferation through deubiquitinating HDAC2.Aging · 2019Article
- New Aspects of HECT-E3 Ligases in Cell Senescence and Cell Death of Plants.Plants (Basel, Switzerland) · 2019Review
- Meta-analysis of gene expression alterations and clinical significance of the HECT domain-containing ubiquitin ligase HUWE1 in cancer.Oncology letters · 2019Article
- Ubiquitination by HUWE1 in tumorigenesis and beyond.Journal of biomedical science · 2018Review
- Review
- Mcl-1 Phosphorylation without Degradation Mediates Sensitivity to HDAC Inhibitors by Liberating BH3-Only Proteins.Cancer research · 2018Article
- Tricho-rhino-phalangeal syndrome 1 protein functions as a scaffold required for ubiquitin-specific protease 4-directed histone deacetylase 2 de-ubiquitination and tumor growth.Breast cancer research : BCR · 2018Article
- Destabilization of Atoh1 by E3 Ubiquitin Ligase Huwe1 and Casein Kinase 1 Is Essential for Normal Sensory Hair Cell Development.The Journal of biological chemistry · 2016Article
- Return to quiescence of mouse neural stem cells by degradation of a proactivation protein.Science (New York, N.Y.) · 2016Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Histone deacetylases (HDACs) are major epigenetic modulators involved in a broad spectrum of human diseases including cancers. Administration of HDAC inhibitors (HDACis) leads to growth inhibition, differentiation, and apoptosis of cancer cells. Understanding the regulatory mechanism of HDACs is imperative to harness the therapeutic potentials of HDACis. Here we show that HDACi- and DNA damage-induced apoptosis are severely compromised in mouse embryonic fibroblasts lacking a HECT domain ubiquitin ligase, Mule (Mcl-1 ubiquitin ligase E3). Mule specifically targets HDAC2 for ubiquitination and degradation. Accumulation of HDAC2 in Mule-deficient cells leads to compromised p53 acetylation as well as crippled p53 transcriptional activation, accumulation, and apoptotic response upon DNA damage and Nutlin-3 treatments. These defects in Mule-null cells can be partially reversed by HDACis and fully rescued by lowering the elevated HDAC2 in Mule-null cells to the normal levels as in wild-type cells. Taken together, our results reveal a critical regulatory mechanism of HDAC2 by Mule and suggest this pathway determines the cellular response to HDACis and DNA damage.
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What OpenQuestion holds
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.