ArticleComputational and structural biotechnology journal2022
POT1-TPP1 binding stabilizes POT1, promoting efficient telomere maintenance.
Article in Computational and structural biotechnology journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 28 citations in OpenAlex.
- Beyond End Protection: Shelterin, POT1 Dysfunction, and Telomere Replication Stress in Cancer.Biomolecules · 2026Review
- Genetic Determinants of Telomere Length and Their Role in Human Disease: Molecular Mechanisms and Underrepresented Populations' Perspectives.Biomedicines · 2026Review
- Active telomere elongation by a subclass of cancer-associated POT1 mutations.Genes & development · 2025Article
- Article
- Structural Motifs at the Telomeres and Their Role in Regulatory Pathways.Biochemistry · 2024Review
- Silencing PinX1 enhances radiosensitivity and antitumor-immunity of radiotherapy in non-small cell lung cancer.Journal of translational medicine · 2024Article
- GermlineGenes · 2024Review
- Case report: GermlineFrontiers in oncology · 2024Article
- Epigenetic mechanism of Gtl2-miRNAs causes the primitive sheep characteristics found in purebred Merino sheep.Cell & bioscience · 2023Article
- Alternative telomere maintenance mechanism iniScience · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Telomeric POT1-TPP1 binding is critical to telomere maintenance and disruption of this complex may lead to cancer. Current data suggests a reduction of intracellular POT1 levels in the absence of TPP1. Here we provide evidence of POT1 plasticity that contributes to its lack of stability in the absence of TPP1 binding. Structural data reveals inter- and intramolecular POT1C domain flexibility in the absence of TPP1. Thermostability and proteolytic resistance assays show that POT1C and the mutant complex POT1C(Q623H)-TPP1(PBD) are less stable than the wild type POT1C-TPP1(PBD), suggesting that TPP1 binding to POT1 stabilizes POT1C and makes it less accessible to proteasomal degradation in the cell. Disruption of the POT1-TPP1 complex such as through cancer-associated mutations leads to a reduction of intracellular POT1, telomere uncapping, and telomere associated DNA damage response (DDR). DDR in turn leads to senescence or genomic instability and oncogenesis.
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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.