ArticleThe EMBO journal2010
The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses.
Article in The EMBO journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 120 citations in OpenAlex.
- KLHL4 upregulates EGFR signaling to promote the malignant progression of oral squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2025Article
- Temporal and Spatial Characterization of CUL3ACS chemical biology · 2025Article
- The ubiquitination-autophagy axis in cancer therapy resistance: mechanistic insights and therapeutic opportunities.Frontiers in pharmacology · 2025Review
- Death-associated protein kinase 1: a double-edged sword in health and disease.Frontiers in immunology · 2025Review
- Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.Experimental hematology & oncology · 2024Review
- Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease.Translational neurodegeneration · 2024Review
- On the Prevalence and Roles of Proteins Undergoing Liquid-Liquid Phase Separation in the Biogenesis of PML-Bodies.Biomolecules · 2023Article
- Genomic characterization and molecular evolution of human monkeypox viruses.Archives of virology · 2023Article
- Deficiency of Cullin 3, a Protein Encoded by a Schizophrenia and Autism Risk Gene, Impairs Behaviors by Enhancing the Excitability of Ventral Tegmental Area (VTA) DA Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The differentially expressed gene signatures of the Cullin 3-RING ubiquitin ligases in neuroendocrine cancer.Biochemical and biophysical research communications · 2022Article
- Increased Expression of the RBPMS Splice Variants Inhibits Cell Proliferation in Ovarian Cancer Cells.International journal of molecular sciences · 2022Article
- A synthetic KLHL20 ligand to validate CUL3Genes & development · 2022Article
- Cul3-KLHL20 E3 ubiquitin ligase plays a key role in the arms race between HIV-1 Nef and host SERINC5 restriction.Nature communications · 2022Article
- Degradation of DRAK1 by CUL3/SPOP E3 Ubiquitin ligase promotes tumor growth of paclitaxel-resistant cervical cancer cells.Cell death & disease · 2022Article
- The roles of KLHL family members in human cancers.American journal of cancer research · 2022Review
- CUL3 (cullin 3)-mediated ubiquitination and degradation of BECN1 (beclin 1) inhibit autophagy and promote tumor progression.Autophagy · 2021Article
- Control of craniofacial and brain development by Cullin3-RING ubiquitin ligases: Lessons from human disease genetics.Experimental cell research · 2020Review
- Melatonin directly binds and inhibits death-associated protein kinase 1 function in Alzheimer's disease.Journal of pineal research · 2020Article
- The RepID-CRL4 ubiquitin ligase complex regulates metaphase to anaphase transition via BUB3 degradation.Nature communications · 2020Article
- Arabidopsis SINAT Proteins Control Autophagy by Mediating Ubiquitylation and Degradation of ATG13.The Plant cell · 2020Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Death-associated protein kinase (DAPK) was identified as a mediator of interferon (IFN)-induced cell death. How IFN controls DAPK activation remains largely unknown. Here, we identify the BTB-Kelch protein KLHL20 as a negative regulator of DAPK. KLHL20 binds DAPK and Cullin 3 (Cul3) via its Kelch-repeat domain and BTB domain, respectively. The KLHL20-Cul3-ROC1 E3 ligase complex promotes DAPK polyubiquitination, thereby inducing the proteasomal degradation of DAPK. Accordingly, depletion of KLHL20 diminishes DAPK ubiquitination and degradation. The KLHL20-mediated DAPK ubiquitination is suppressed in cells receiving IFN-alpha or IFN-gamma, which induces an enrichment/sequestration of KLHL20 in the PML nuclear bodies, thereby separating KLHL20 from DAPK. Consequently, IFN triggers the stabilization of DAPK. This mechanism of DAPK stabilization is crucial for determining IFN responsiveness of tumor cells and contributes to IFN-induced autophagy. This study identifies KLHL20-Cul3-ROC1 as an E3 ligase for DAPK ubiquitination and reveals a regulatory mechanism of DAPK, through blocking its accessibility to this E3 ligase, in IFN-induced apoptotic and autophagic death. Our findings may be relevant to the problem of IFN resistance in cancer therapy.
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