ArticleOncotarget2016
High Mobility Group A2 protects cancer cells against telomere dysfunction.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Characterization of HMGA2 variants expands the spectrum of Silver-Russell syndrome.JCI insight · 2024Article
- Review
- Nuclear High Mobility Group A2 (HMGA2) Interactome Revealed by Biotin Proximity Labeling.International journal of molecular sciences · 2023Article
- HMGA2 expression defines a subset of human AML with immature transcriptional signature and vulnerability to G2/M inhibition.Blood advances · 2022Article
- Article
- HMGA2 as a functional antagonist of PARP1 inhibitors in tumor cells.Molecular oncology · 2019Article
- Distinct 3D Structural Patterns of Lamin A/C Expression in Hodgkin and Reed-Sternberg Cells.Cancers · 2018Article
- The Linker Histone GH1-HMGA1 Is Involved in Telomere Stability and DNA Damage Repair.Plant physiology · 2018Article
- Increased high-mobility group A2 correlates with lymph node metastasis and prognosis of non-small cell lung cancer.Cancer biomarkers : section A of Disease markers · 2018Article
- Increased high mobility group A 2 expression promotes transition of cervical intraepithelial neoplasm into cervical cancer.Oncotarget · 2018Article
- Reactive Oxygen Species-Mediated Tumor Microenvironment Transformation: The Mechanism of Radioresistant Gastric Cancer.Oxidative medicine and cellular longevity · 2018Review
- Nanoscale Assembly of High-Mobility Group AT-Hook 2 Protein with DNA Replication Fork.Biophysical journal · 2017Article
- Ubiquitin C-terminal hydrolase isozyme L1 is associated with shelterin complex at interstitial telomeric sites.Epigenetics & chromatin · 2017Article
- A panel of four genes accurately differentiates benign from malignant thyroid nodules.Journal of experimental & clinical cancer research : CR · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The non-histone chromatin binding protein High Mobility Group AT-hook protein 2 (HMGA2) plays important roles in the repair and protection of genomic DNA in embryonic stem cells and cancer cells. Here we show that HMGA2 localizes to mammalian telomeres and enhances telomere stability in cancer cells. We present a novel interaction of HMGA2 with the key shelterin protein TRF2. We found that the linker (L1) region of HMGA2 contributes to this interaction but the ATI-L1-ATII molecular region of HMGA2 is required for strong interaction with TRF2. This interaction was independent of HMGA2 DNA-binding and did not require the TRF2 interacting partner RAP1 but involved the homodimerization and hinge regions of TRF2. HMGA2 retained TRF2 at telomeres and reduced telomere-dysfunction despite induced telomere stress. Silencing of HMGA2 resulted in (i) reduced binding of TRF2 to telomere DNA as observed by ChIP, (ii) increased telomere instability and (iii) the formation of telomere dysfunction-induced foci (TIF). This resulted in increased telomere aggregation, anaphase bridges and micronuclei. HMGA2 prevented ATM-dependent pTRF2T188 phosphorylation and attenuated signaling via the telomere specific ATM-CHK2-CDC25C DNA damage signaling axis. In summary, our data demonstrate a unique and novel role of HMGA2 in telomere protection and promoting telomere stability in cancer cells. This identifies HMGA2 as a new therapeutic target for the destabilization of telomeres in HMGA2+ cancer 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.