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Article

MED28 Over-Expression Shortens the Cell Cycle and Induces Genomic Instability

1
Department of Pharmacy, College of Pharmacy, Ajou University, 206 World Cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 16499, Korea
2
College of Pharmacy, Daegu Catholic University, Hayang-ro 13-13, Hayang-eup, Gyeongsan-si, Gyeongbuk 38430, Korea
3
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea
4
Genomic Instability Research Center, Ajou University School of Medicine, Suwon 16499, Korea
5
Department of Biomedical Science, Graduate School of Ajou University, Suwon 16499, Korea
6
Department of Molecular Biology, Dankook University, Cheonan-si, Chungnam 31116, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(7), 1746; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071746
Received: 20 March 2019 / Revised: 6 April 2019 / Accepted: 8 April 2019 / Published: 9 April 2019
(This article belongs to the Section Biochemistry)
The mammalian mediator complex subunit 28 (MED28) is overexpressed in a variety of cancers and it regulates cell migration/invasion and epithelial-mesenchymal transition. However, transcription factors that increase MED28 expression have not yet been identified. In this study, we performed a luciferase reporter assay to identify and characterize the prospective transcription factors, namely E2F transcription factor 1, nuclear respiratory factor 1, E-26 transforming sequence 1, and CCAAT/enhancer-binding protein β, which increased MED28 expression. In addition, the release from the arrest at the G1−S or G2−M phase transition after cell cycle synchronization using thymidine or nocodazole, respectively, showed enhanced MED28 expression at the G1−S transition and mitosis. Furthermore, the overexpression of MED28 significantly decreased the duration of interphase and mitosis. Conversely, a knockdown of MED28 using si-RNA increased the duration of interphase and mitosis. Of note, the overexpression of MED28 significantly increased micronucleus and nuclear budding in HeLa cells. In addition, flow cytometry and fluorescence microscopy analyses showed that the overexpression of MED28 significantly increased aneuploid cells. Taken together, these results suggest that MED28 expression is increased by oncogenic transcription factors and its overexpression disturbs the cell cycle, which results in genomic instability and aneuploidy. View Full-Text
Keywords: aneuploidy; cell cycle; transcription factor; micronucleus; nuclear budding aneuploidy; cell cycle; transcription factor; micronucleus; nuclear budding
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MDPI and ACS Style

Cho, J.G.; Choi, J.-S.; Lee, J.-H.; Cho, M.-G.; Kim, H.-S.; Noh, H.-D.; Lim, K.-H.; Park, B.; Kim, J.-O.; Park, S.G. MED28 Over-Expression Shortens the Cell Cycle and Induces Genomic Instability. Int. J. Mol. Sci. 2019, 20, 1746. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071746

AMA Style

Cho JG, Choi J-S, Lee J-H, Cho M-G, Kim H-S, Noh H-D, Lim K-H, Park B, Kim J-O, Park SG. MED28 Over-Expression Shortens the Cell Cycle and Induces Genomic Instability. International Journal of Molecular Sciences. 2019; 20(7):1746. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071746

Chicago/Turabian Style

Cho, Jin G., Joon-Seok Choi, Jae-Ho Lee, Min-Guk Cho, Hong-Sook Kim, Hee-Dong Noh, Key-Hwan Lim, Byoungjun Park, Jin-Ock Kim, and Sang G. Park 2019. "MED28 Over-Expression Shortens the Cell Cycle and Induces Genomic Instability" International Journal of Molecular Sciences 20, no. 7: 1746. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071746

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