ArticleProceedings of the National Academy of Sciences of the United States of America2015
INK4 locus of the tumor-resistant rodent, the naked mole rat, expresses a functional p15/p16 hybrid isoform.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 104 citations in OpenAlex.
- Intrinsic anti-tumorigenic properties of the skin epithelium promote cancer resistance in naked mole-rats.iScience · 2026Article
- Unlocking longevity through the comparative biology of aging.Nature aging · 2025Review
- A Trade-Off between Body Mass and Cancer Resistance in Cetaceans Is Mediated by Cell Cycle-Related Gene Evolution.Molecular biology and evolution · 2025Article
- Dynamics of epithelial-mesenchymal plasticity driving cancer drug resistance.Cancer pathogenesis and therapy · 2025Review
- Utilisation of High Molecular Weight and Ultra-High Molecular Weight Hyaluronan in Management of Glioblastoma.Gels (Basel, Switzerland) · 2025Review
- Comparative time-series multi-omics analyses suggest H1.2 involvement in anoxic adaptation and cancer resistance.PLoS biology · 2024Article
- Review
- Adult stem cell activity in naked mole rats for long-term tissue maintenance.Nature communications · 2023Article
- Integration of fluorescence in situ hybridization and chromosome-length genome assemblies revealed synteny map for guinea pig, naked mole-rat, and human.Scientific reports · 2023Article
- Hyaluronic Acid as a Modern Approach in Anticancer Therapy-Review.International journal of molecular sciences · 2022Review
- Review
- Carcinogenesis resistance in the longest-lived rodent, the naked mole-rat.Cancer science · 2022Review
- Is Aging an Inevitable Characteristic of Organic Life or an Evolutionary Adaptation?Biochemistry. Biokhimiia · 2022Review
- Skin Aging in Long-Lived Naked Mole-Rats Is Accompanied by Increased Expression of Longevity-Associated and Tumor Suppressor Genes.The Journal of investigative dermatology · 2022Article
- Characterization of naked mole-rat hematopoiesis reveals unique stem and progenitor cell patterns and neotenic traits.The EMBO journal · 2022Article
- Bodyweight, locomotion, and behavioral responses of the naked mole rat (Heterocephalus glaber) to lipopolysaccharide administration.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2022Article
- Dissecting and Reconstructing Matrix in Malignant Mesothelioma Through Histocell-Histochemistry Gradients for Clinical Applications.Frontiers in medicine · 2022Article
- A phylogenetic review of cancer resistance highlights evolutionary solutions to Peto's Paradox.Genetics and molecular biology · 2022Article
- The hypoxia adaptation of small mammals to plateau and underground burrow conditions.Animal models and experimental medicine · 2021Review
- Revelations About Aging and Disease from Unconventional Vertebrate Model Organisms.Annual review of genetics · 2021Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The naked mole rat (Heterocephalus glaber) is a long-lived and tumor-resistant rodent. Tumor resistance in the naked mole rat is mediated by the extracellular matrix component hyaluronan of very high molecular weight (HMW-HA). HMW-HA triggers hypersensitivity of naked mole rat cells to contact inhibition, which is associated with induction of the INK4 (inhibitors of cyclin dependent kinase 4) locus leading to cell-cycle arrest. The INK4a/b locus is among the most frequently mutated in human cancer. This locus encodes three distinct tumor suppressors: p15(INK4b), p16(INK4a), and ARF (alternate reading frame). Although p15(INK4b) has its own ORF, p16(INK4a) and ARF share common second and third exons with alternative reading frames. Here, we show that, in the naked mole rat, the INK4a/b locus encodes an additional product that consists of p15(INK4b) exon 1 joined to p16(INK4a) exons 2 and 3. We have named this isoform pALT(INK4a/b) (for alternative splicing). We show that pALT(INK4a/b) is present in both cultured cells and naked mole rat tissues but is absent in human and mouse cells. Additionally, we demonstrate that pALT(INK4a/b) expression is induced during early contact inhibition and upon a variety of stresses such as UV, gamma irradiation-induced senescence, loss of substrate attachment, and expression of oncogenes. When overexpressed in naked mole rat or human cells, pALT(INK4a/b) has stronger ability to induce cell-cycle arrest than either p15(INK4b) or p16(INK4a). We hypothesize that the presence of the fourth product, pALT(INK4a/b) of the INK4a/b locus in the naked mole rat, contributes to the increased resistance to tumorigenesis of this species.
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