ArticleNeoplasia (New York, N.Y.)2011
Identification and characterization of KCASH2 and KCASH3, 2 novel Cullin3 adaptors suppressing histone deacetylase and Hedgehog activity in medulloblastoma.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 92 citations in OpenAlex.
- A Global Analysis of the Complex Structural Organization of KCTD Proteins and Their Functional Implications.International journal of molecular sciences · 2026Review
- SMURF1 and SMURF2 directly target GLI1 for ubiquitination and proteasome-dependent degradation.Cell death discovery · 2024Article
- KCTD1 regulation of Adenylyl cyclase type 5 adjusts striatal cAMP signaling.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- A Comprehensive Analysis of the Structural Recognition between KCTD Proteins and Cullin 3.International journal of molecular sciences · 2024Article
- SALL4 is a CRL3Cell death and differentiation · 2024Article
- Article
- KCTD1 is a new modulator of the KCASH family of Hedgehog suppressors.Neoplasia (New York, N.Y.) · 2023Article
- Calpain activity is negatively regulated by a KCTD7-Cullin-3 complex via non-degradative ubiquitination.Cell discovery · 2023Article
- Epigenetics and immune cells in medulloblastoma.Frontiers in genetics · 2023Review
- Alphafold Predictions Provide Insights into the Structural Features of the Functional Oligomers of All Members of the KCTD Family.International journal of molecular sciences · 2022Article
- Advances in glioma-associated oncogene (GLI) inhibitors for cancer therapy.Investigational new drugs · 2022Review
- Review
- Insights Into the Properties, Biological Functions, and Regulation of USP21.Frontiers in pharmacology · 2022Review
- AlphaFold-Predicted Structures of KCTD Proteins Unravel Previously Undetected Relationships among the Members of the Family.Biomolecules · 2021Article
- Identification of Prognostic Gene Biomarkers in Non-Small Cell Lung Cancer Progression by Integrated Bioinformatics Analysis.Biology · 2021Article
- Proteasomal Degradation of Zn-Dependent Hdacs: The E3-Ligases Implicated and the Designed Protacs That Enable Degradation.Molecules (Basel, Switzerland) · 2021Review
- The emerging role of the KCTD proteins in cancer.Cell communication and signaling : CCS · 2021Review
- KCTD19 and its associated protein ZFP541 are independently essential for meiosis in male mice.PLoS genetics · 2021Article
- Specific Protein 1 and p53 Interplay Modulates the Expression of the KCTD-Containing Cullin3 Adaptor Suppressor of Hedgehog 2.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Medulloblastoma is the most common pediatric malignant brain tumor, arising from aberrant cerebellar precursors' development, a process mainly controlled by Hedgehog (Hh) signaling pathway. Histone deacetylase HDAC1 has been recently shown to modulate Hh signaling, deacetylating its effectors Gli1/2 and enhancing their transcriptional activity. Therefore, HDAC may represent a potential therapeutic target for Hh-dependent tumors, but still little information is available on the physiological mechanisms of HDAC regulation. The putative tumor suppressor REN(KCTD11) acts through ubiquitination-dependent degradation of HDAC1, thereby affecting Hh activity and medulloblastoma growth. We identify and characterize here two REN(KCTD11) homologues, defining a new family of proteins named KCASH, as "KCTD containing, Cullin3 adaptor, suppressor of Hedgehog." Indeed, the novel genes (KCASH2(KCTD21) and KCASH3(KCTD6)) share with REN(KCTD11) a number of features, such as a BTB domain required for the formation of a Cullin3 ubiquitin ligase complex and HDAC1 ubiquitination and degradation capability, suppressing the acetylation-dependent Hh/Gli signaling. Expression of KCASH2 and -3 is observed in cerebellum, whereas epigenetic silencing and allelic deletion are observed in human medulloblastoma. Rescuing KCASHs expression reduces the Hedgehog-dependent medulloblastoma growth, suggesting that loss of members of this novel family of native HDAC inhibitors is crucial in sustaining Hh pathway-mediated tumorigenesis. Accordingly, they might represent a promising class of endogenous "agents" through which this pathway may be targeted.
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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.