ArticleCancer research2010
Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 168 citations in OpenAlex.
- RNA modifications as determinants of cancer cell death: from epitranscriptomic mechanisms to therapeutic targeting.Functional & integrative genomics · 2026Review
- DKC1: a robust prognostic factor and potential therapeutic target in multiple myeloma.Journal of translational medicine · 2026Article
- RNA modifications in cancer: from biological insights to therapeutic targets.Bioorganic & medicinal chemistry · 2026Review
- Integrative Genomic Analysis Reveals Pseudouridine Modification-Related Gene Signatures Associated With Prognosis and Therapeutic Response Patterns in Hepatocellular Carcinoma.International journal of genomics · 2026Article
- Dyskerin dysfunction in cancer development: from telomere dysregulation to immune deficiency.American journal of cancer research · 2026Review
- DKC1-mediated pseudouridylation of rRNA targets hnRNP A1 to sustain IRES-dependent translation and ATF4-driven metabolic adaptation.Science advances · 2025Article
- Structural basis for hygromycin B inhibition of yeast pseudouridine-deficient ribosomes.Science advances · 2025Article
- Functional screen identifies RBM42 as a mediator of oncogenic mRNA translation specificity.Nature cell biology · 2025Article
- The zebrafish (NAR genomics and bioinformatics · 2025Article
- Review
- SNORD113-114 cluster maintains haematopoietic stem cell self-renewal via orchestrating the translation machinery.Nature cell biology · 2025Article
- Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.Experimental hematology & oncology · 2025Review
- Implications of RNA pseudouridylation for cancer biology and therapeutics: a narrative review.Journal of translational medicine · 2024Review
- Decoding the 'Fifth' Nucleotide: Impact of RNA Pseudouridylation on Gene Expression and Human Disease.Molecular biotechnology · 2024Review
- Decoding the ribosome's hidden language: rRNA modifications as key players in cancer dynamics and targeted therapies.Clinical and translational medicine · 2024Review
- RNA methylation-related inhibitors: Biological basis and therapeutic potential for cancer therapy.Clinical and translational medicine · 2024Review
- Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment.Journal of pharmaceutical analysis · 2024Review
- Advancements in pseudouridine modifying enzyme and cancer.Frontiers in cell and developmental biology · 2024Review
- RNA modifications in gynecological cancer: current status and future directions.Frontiers in medicine · 2024Review
- The RNA-Binding Function of Ribosomal Proteins and Ribosome Biogenesis Factors in Human Health and Disease.Biomedicines · 2023Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Mutations in DKC1, encoding for dyskerin, a pseudouridine synthase that modifies rRNA and regulates telomerase activity, are associated with ribosomal dysfunction and increased cancer susceptibility in the human syndrome, X-linked dyskeratosis congenita (X-DC). In a mouse model for X-DC, impairments in DKC1 function affected the translation of specific mRNAs harboring internal ribosomal entry site (IRES) elements, including the tumor suppressor, p27. However, how this translational deregulation contributes to tumor initiation and progression remains poorly understood. Here, we report that impairment in p27 IRES-mediated translation due to decreased levels of DKC1 activity markedly increases spontaneous pituitary tumorigenesis in p27 heterozygous mice. Using a new bioluminescent mouse model, we monitored p27 translation in vivo and show that p27 IRES-mediated translation is reduced in the pituitary of DKC1 hypomorphic mice (DKC1(m)). Furthermore, we show that DKC1 has a critical role in regulating the assembly of the 48S translational preinitiation complex mediated by the p27 IRES element. An analysis of human tumors identified a novel mutation of DKC1 (DKC1(S485G)) in a human pituitary adenoma. We show that this specific amino acid substitution significantly alters DKC1 stability/pseudouridylation activity, and this correlates with reductions in p27 protein levels. Furthermore, DKC1(S485G) mutation does not alter telomerase RNA levels. Altogether, these findings show that genetic alterations in DKC1 could contribute to tumorigenesis associated with somatic cancers and establish a critical role for DKC1 in tumor suppression, at least in part, through translational control of p27.
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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.