ArticleNucleic acids research2003
High mobility group A2 protein and its derivatives bind a specific region of the promoter of DNA repair gene ERCC1 and modulate its activity.
Article in Nucleic acids research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- High mobility group A protein-2 as a tumor cancer diagnostic and prognostic marker: a systematic review and meta-analysis.European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) · 2020Pooled it
- Decoding high mobility group A2 protein expression regulation and implications in human cancers.Discover oncology · 2024Review
- Detection of oxaliplatin- and cisplatin-DNA lesions requires different global genome repair mechanisms that affect their clinical efficacy.NAR cancer · 2023Article
- MicroRNA-9-5p increases the sensitivity of colorectal cancer cells to 5-fluorouracil by downregulating high mobility group A2 expression.Oncology letters · 2021Article
- Review
- High Mobility Group AT-Hook 2 (HMGA2) Oncogenicity in Mesenchymal and Epithelial Neoplasia.International journal of molecular sciences · 2020Review
- MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC.Journal of hematology & oncology · 2020Article
- miR-16 regulates proliferation and apoptosis of pituitary adenoma cells by inhibiting HMGA2.Oncology letters · 2019Article
- Loss of CDX2 gene expression is associated with DNA repair proteins and is a crucial member of the Wnt signaling pathway in liver metastasis of colorectal cancer.Oncology letters · 2018Article
- Effect of RNA interference of the expression of HMGA2 on the proliferation and invasion ability of ACHN renal cell carcinoma cells.Molecular medicine reports · 2017Article
- Critical role of HMGA proteins in cancer cell chemoresistance.Journal of molecular medicine (Berlin, Germany) · 2017Review
- TWIST1 drives cisplatin resistance and cell survival in an ovarian cancer model, via upregulation of GAS6, L1CAM, and Akt signalling.Scientific reports · 2016Article
- The Architectural Chromatin Factor High Mobility Group A1 Enhances DNA Ligase IV Activity Influencing DNA Repair.PloS one · 2016Article
- HMGA2 Expression in Renal Carcinoma and its Clinical Significance.Journal of medical biochemistry · 2015Article
- Epigenetic reduction of DNA repair in progression to gastrointestinal cancer.World journal of gastrointestinal oncology · 2015Article
- Transcriptome profiling identifies HMGA2 as a biomarker of melanoma progression and prognosis.The Journal of investigative dermatology · 2013Article
- HMGA2 and high-grade serous ovarian carcinoma.Journal of molecular medicine (Berlin, Germany) · 2013Review
- Three-dimensional collagen I promotes gemcitabine resistance in pancreatic cancer through MT1-MMP-mediated expression of HMGA2.Cancer research · 2011Article
- HMGA2 exhibits dRP/AP site cleavage activity and protects cancer cells from DNA-damage-induced cytotoxicity during chemotherapy.Nucleic acids research · 2009Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High mobility group A2 (HMGA2) chromosomal non-histone protein and its derivatives play an important role in development and progression of benign and malignant tumors, obesity and arteriosclerosis, although the underlying mechanisms of these conditions are poorly understood. Therefore, we tried to identify target genes for this transcriptional regulator and to provide insights in the mechanism of interaction to its target. Multiple genes have been identified by microarray experiments as being transcriptionally regulated by HMGA2. Among these we chose the ERCC1 gene, encoding a DNA repair protein, for this study. DNA-binding studies were performed using HMGA2 and C-terminally truncated DeltaHMGA2, a derivative that is frequently observed in a variety of tumors. A unique high affinity HMGA2 binding site was mapped to a specific AT-rich region located -323 to -298 upstream of the ERCC1 transcription start site, distinguishing it from other potential AT-rich binding sites. The observed 1:1 stoichiometry for the binding of wild-type HMGA2 to this region was altered to 1:2 upon binding of truncated DeltaHMGA2, causing DNA bending. Furthermore, the regulatory effect of HMGA2 was confirmed by luciferase promoter assays showing that ERCC1 promoter activity is down-regulated by all investigated HMGA2 forms, with the most striking effect exerted by DeltaHMGA2. Our results provide the first insights into how HMGA2 and its aberrant forms bind and regulate the ERCC1 promoter.
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