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Title: Cell-based high-throughput compound screening reveals functional interaction between oncofetal HMGA2 and topoisomerase I
Authors: Peter, Sabrina
Yu, Haojie
Ivanyi-Nagy, Roland
Dröge, Peter
Keywords: Topoisomerase
DRNTU::Science::Biological sciences
Issue Date: 2016
Source: Peter, S., Yu, H., Ivanyi-Nagy, R., & Dröge, P. (2016). Cell-based high-throughput compound screening reveals functional interaction between oncofetal HMGA2 and topoisomerase I. Nucleic Acids Research, 44(22), e162-. doi:10.1093/nar/gkw759
Series/Report no.: Nucleic Acids Research
Abstract: HMGA2 is an important chromatin factor that interacts with DNA via three AT-hook domains, thereby regulating chromatin architecture and transcription during embryonic and fetal development. The protein is absent from differentiated somatic cells, but aberrantly re-expressed in most aggressive human neoplasias where it is causally linked to cell transformation and metastasis. DNA-binding also enables HMGA2 to protect cancer cells from DNA-damaging agents. HMGA2 therefore is considered to be a prime drug target for many aggressive malignancies. Here, we have developed a broadly applicable cell-based reporter system which can identify HMGA2 antagonists targeting functionally important protein domains, as validated with the known AT-hook competitor netropsin. In addition, high-throughput screening can uncover functional links between HMGA2 and cellular factors important for cell transformation. This is demonstrated with the discovery that HMGA2 potentiates the clinically important topoisomerase I inhibitor irinotecan/SN-38 in trapping the enzyme in covalent DNA-complexes, thereby attenuating transcription.
ISSN: 0305-1048
Rights: © 2016 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact
Fulltext Permission: open
Fulltext Availability: With Fulltext
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