ArticleThe Journal of cell biology2007
Lack of TRF2 in ALT cells causes PML-dependent p53 activation and loss of telomeric DNA.
Article in The Journal of cell biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- The Altered Functions of Shelterin Components in ALT Cells.International journal of molecular sciences · 2023Review
- Telomerase-targeted therapies in myeloid malignancies.Blood advances · 2023Review
- TZAP overexpression induces telomere dysfunction and ALT-like activity in ATRX/DAXX-deficient cells.iScience · 2023Article
- Potential clinical treatment prospects behind the molecular mechanism of alternative lengthening of telomeres (ALT).Journal of Cancer · 2023Review
- RNA 5-methylcytosine status is associated with DNMT2/TRDMT1 nuclear localization in osteosarcoma cell lines.Journal of bone oncology · 2022Article
- Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells.Scientific reports · 2021Article
- The regulatory roles of p53 in cardiovascular health and disease.Cellular and molecular life sciences : CMLS · 2021Review
- Cyclic Peptidic Mimetics of Apollo Peptides Targeting Telomeric Repeat Binding Factor 2 (TRF2) and Apollo Interaction.ACS medicinal chemistry letters · 2018Article
- Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex.Scientific reports · 2017Article
- Withaferin-A kills cancer cells with and without telomerase: chemical, computational and experimental evidences.Cell death & disease · 2017Article
- Means to the ends: The role of telomeres and telomere processing machinery in metastasis.Biochimica et biophysica acta · 2016Review
- Review
- Article
- Molecular targeting of TRF2 suppresses the growth and tumorigenesis of glioblastoma stem cells.Glia · 2014Article
- The basic N-terminal domain of TRF2 limits recombination endonuclease action at human telomeres.Cell cycle (Georgetown, Tex.) · 2014Article
- The telomere-associated homeobox-containing protein TAH1/HMBOX1 participates in telomere maintenance in ALT cells.Journal of cell science · 2013Article
- Gene expression levels of human shelterin complex and shelterin-associated factors regulated by the topoisomerase II inhibitors doxorubicin and etoposide in human cultured cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- BRCA2 is epistatic to the RAD51 paralogs in response to DNA damage.DNA repair · 2013Article
- p300-mediated acetylation of TRF2 is required for maintaining functional telomeres.Nucleic acids research · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Alternative lengthening of telomere (ALT) tumors maintain telomeres by a telomerase-independent mechanism and are characterized by a nuclear structure called the ALT-associated PML body (APB). TRF2 is a component of a telomeric DNA/protein complex called shelterin. However, TRF2 function in ALT cells remains elusive. In telomerase-positive tumor cells, TRF2 inactivation results in telomere de-protection, activation of ATM, and consequent induction of p53-dependent apoptosis. We show that in ALT cells this sequence of events is different. First, TRF2 inactivation/silencing does not induce cell death in p53-proficient ALT cells, but rather triggers cellular senescence. Second, ATM is constitutively activated in ALT cells and colocalizes with TRF2 into APBs. However, it is only following TRF2 silencing that the ATM target p53 is activated. In this context, PML is indispensable for p53-dependent p21 induction. Finally, we find a substantial loss of telomeric DNA upon stable TRF2 knockdown in ALT cells. Overall, we provide insight into the functional consequences of shelterin alterations in ALT cells.
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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.