ArticleOncogene2015
KLHL39 suppresses colon cancer metastasis by blocking KLHL20-mediated PML and DAPK ubiquitination.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- IVNS1ABP mutation drives cellular senescence in newly identified progeroid neuropathy.Nature communications · 2026Article
- KLHL4 upregulates EGFR signaling to promote the malignant progression of oral squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2025Article
- NS1 binding protein regulates stress granule dynamics and clearance by inhibiting p62 ubiquitination.Nature communications · 2024Article
- Anoikis-related signature identifies tumor microenvironment landscape and predicts prognosis and drug sensitivity in colorectal cancer.Journal of Cancer · 2024Article
- Kelch-like proteins in the gastrointestinal tumors.Acta pharmacologica Sinica · 2023Review
- A synthetic KLHL20 ligand to validate CUL3Genes & development · 2022Article
- A novel HIF1α-STIL-FOXM1 axis regulates tumor metastasis.Journal of biomedical science · 2022Article
- The roles of KLHL family members in human cancers.American journal of cancer research · 2022Review
- Targeted protein degradation: expanding the toolbox.Nature reviews. Drug discovery · 2019Article
- Expression of long non-coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple-negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death.Molecular oncology · 2019Article
- Structural-functional interactions of NS1-BP protein with the splicing and mRNA export machineries for viral and host gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Crystal structure of the Kelch domain of human NS1-binding protein at 1.98 Å resolution.Acta crystallographica. Section F, Structural biology communications · 2018Article
- Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and Potential Targeting for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
- Functional analysis of Cullin 3 E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2018Review
- Ubiquitination of tumor suppressor PML regulates prometastatic and immunosuppressive tumor microenvironment.The Journal of clinical investigation · 2017Article
- Article
- Identification of expression patterns in the progression of disease stages by integration of transcriptomic data.BMC bioinformatics · 2016Article
- Cul3-KLHL20 ubiquitin ligase: physiological functions, stress responses, and disease implications.Cell division · 2016Review
- Cullin 3 Ubiquitin Ligases in Cancer Biology: Functions and Therapeutic Implications.Frontiers in oncology · 2016Review
- The function, regulation and therapeutic implications of the tumor suppressor protein, PML.Cell & bioscience · 2015Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cullin 3 (Cul3)-family ubiquitin ligases use the BTB-domain-containing proteins for the recruitment of substrates, but the regulation of this family of ubiquitin ligases has not been completely understood. KLHL20 is a BTB-family protein and targets tumor suppressor promyelocytic leukemia protein (PML) and death-associated protein kinase (DAPK) to its kelch-repeat domain for ubiquitination and degradation. Here, we show that another BTB-kelch protein KLHL39 is recruited to the substrate-binding domain of KLHL20 but is not a substrate of Cul3-KLHL20 complex. Interestingly, KLHL39 does not bind Cul3 because of the absence of certain conserved residues in the BTB domain. Instead, KLHL39 blocks KLHL20-mediated ubiquitination of PML and DAPK by disrupting the binding of these substrates to KLHL20 as well as the binding of KLHL20 to Cul3. Through the two mechanisms, KLHL39 increases the stability of PML and DAPK. In human colon cancers, downregulations of KLHL39, PML and DAPK are associated with metastatic progression. Furthermore, preclinical data indicate that KLHL39 promotes colon cancer migration, invasion and survival in vitro and metastasis in vivo through a PML- and DAPK-dependent mechanism. Our study identifies KLHL39 as a negative regulator of Cul3-KLHL20 ubiquitin ligase and reveals a role of KLHL39-mediated PML and DAPK stabilization in colon cancer metastasis.
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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.