ArticlePLoS genetics2017
A new mode of DNA binding distinguishes Capicua from other HMG-box factors and explains its mutation patterns in cancer.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 62 citations in OpenAlex.
- Targeting CIC::DUX4 sarcoma with Minnelide in a dual recombinase-initiated genetically engineered mouse model.The Journal of clinical investigation · 2026Article
- Multiomics Profiling During Autoimmune Demyelination Highlights a Complex Regulatory Role for Ataxin-1 in B Cells.Annals of the New York Academy of Sciences · 2026Article
- Modeling of Capicua Family Fusion Oncoprotein-Driven Cancers Reveals Gene-Specific Functionality.Molecular cancer research : MCR · 2026Article
- ERK inhibits Capicua repressor function via multisite phosphorylation.Journal of cell science · 2026Article
- Molecular basis of DNA recognition by the HMG-box-C1 module of capicua.Structure (London, England : 1993) · 2025Article
- Efficacy of Minnelide in a Next-Generation Dual-Recombinase Regulated Genetically Engineered Mouse Model of CIC::DUX4 Sarcoma.bioRxiv : the preprint server for biology · 2025Article
- Upregulation of POLE and proficient DNA repair are features of CIC::DUX4 sarcomas.NPJ precision oncology · 2025Article
- Article
- Transcriptional repressor Capicua is a gatekeeper of cell-intrinsic interferon responses.Cell host & microbe · 2025Article
- The capicua-ataxin-1-like complex regulates Notch-driven marginal zone B cell development and sepsis progression.Nature communications · 2024Article
- The Capicua C1 Domain Is Required for Full Activity of the CIC::DUX4 Fusion Oncoprotein.Cancer research communications · 2024Article
- ThebioRxiv : the preprint server for biology · 2024Article
- Molecular and therapeutic advancements in Capicua (Frontiers in cell and developmental biology · 2024Review
- CIC reduces xCT/SLC7A11 expression and glutamate release in glioma.Acta neuropathologica communications · 2023Article
- CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers.Cancers · 2022Review
- Noncanonical function of Capicua as a growth termination signal inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Integrated proteomic analysis of low-grade gliomas reveals contributions of 1p-19q co-deletion to oligodendroglioma.Acta neuropathologica communications · 2022Article
- ERK phosphorylation disrupts the intramolecular interaction of capicua to promote cytoplasmic translocation of capicua and tumor growth.Frontiers in molecular biosciences · 2022Article
- Capicua is a fast-acting transcriptional brake.Current biology : CB · 2021Article
- LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia.Molecular psychiatry · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HMG-box proteins, including Sox/SRY (Sox) and TCF/LEF1 (TCF) family members, bind DNA via their HMG-box. This binding, however, is relatively weak and both Sox and TCF factors employ distinct mechanisms for enhancing their affinity and specificity for DNA. Here we report that Capicua (CIC), an HMG-box transcriptional repressor involved in Ras/MAPK signaling and cancer progression, employs an additional distinct mode of DNA binding that enables selective recognition of its targets. We find that, contrary to previous assumptions, the HMG-box of CIC does not bind DNA alone but instead requires a distant motif (referred to as C1) present at the C-terminus of all CIC proteins. The HMG-box and C1 domains are both necessary for binding specific TGAATGAA-like sites, do not function via dimerization, and are active in the absence of cofactors, suggesting that they form a bipartite structure for sequence-specific binding to DNA. We demonstrate that this binding mechanism operates throughout Drosophila development and in human cells, ensuring specific regulation of multiple CIC targets. It thus appears that HMG-box proteins generally depend on auxiliary DNA binding mechanisms for regulating their appropriate genomic targets, but that each sub-family has evolved unique strategies for this purpose. Finally, the key role of C1 in DNA binding also explains the fact that this domain is a hotspot for inactivating mutations in oligodendroglioma and other tumors, while being preserved in oncogenic CIC-DUX4 fusion chimeras associated to Ewing-like sarcomas.
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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.