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KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity

  • Authors:
    • Shirin Jamshidi
    • Steven Catchpole
    • Jie Chen
    • Chi Wai Eric So
    • Joy Burchell
    • Khondaker Miraz Rahman
    • Joyce Taylor‑Papadimitriou
  • View Affiliations / Copyright

    Affiliations: Institute of Pharmaceutical Science, School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 9NN, UK, Breast Cancer Biology, Innovation Hub, School of Cancer and Pharmaceutical Sciences, King's College London, Guy's Cancer Centre, Guy's Hospital, London SE1 9RT, UK, Leukaemia and Stem Cell Biology Group, School of Cancer and Pharmaceutical Sciences, Denmark Hill Campus, King's College London, London SE5 9RJ, UK
    Copyright: © Jamshidi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 96
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    Published online on: October 27, 2021
       https://doi.org/10.3892/ijo.2021.5276
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Abstract

Post‑translational modification of histones serve a crucial role in the control of gene transcription. Trimethylation of lysine 4 on histone 3 is associated with transcription activation. There are currently six known methylases and six known demethylases that can control the methylation status of this site. Lysine demethylase 5B (KDM5B) is one such demethylase, which can repress gene expression. In particular KDM5B has been found to be overexpressed in a number of cancer types, and small‑molecular weight inhibitors of its demethylase activity have been identified. Previous characterisation of Kdm5b knock‑out mice has revealed that this genotype leads to either embryonic or neonatal lethality. However, the ΔA‑T rich interaction domain (ΔARID)‑KDM5B strain of mice, which have the ARID domain and five amino acids within the Jumonji (Jmj)N domain spliced out from KDM5B, remain viable and fertile. In the present study, ΔARID‑KDM5B was found to have no demethylase activity as determined by in vitro demethylase assays and by immunofluorescence in transfected Cos‑1 cells. Furthermore, molecular dynamic simulations revealed conformational changes within the ΔARID‑KDM5B structure compared with that in WT‑KDM5B, particularly in the JmjC domain, which is responsible for the catalytic activity of WT‑KDM5B. This supports the experimental data that shows the loss of demethylase activity. Since Kdm5b knock‑out mice show varying degrees of lethality, these data suggest that KDM5B serves a crucial function in development in a manner that is independent of its demethylase activity.
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Copy and paste a formatted citation
Spandidos Publications style
Jamshidi S, Catchpole S, Chen J, So CW, Burchell J, Rahman KM and Taylor‑Papadimitriou J: KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity. Int J Oncol 59: 96, 2021.
APA
Jamshidi, S., Catchpole, S., Chen, J., So, C.W., Burchell, J., Rahman, K.M., & Taylor‑Papadimitriou, J. (2021). KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity. International Journal of Oncology, 59, 96. https://doi.org/10.3892/ijo.2021.5276
MLA
Jamshidi, S., Catchpole, S., Chen, J., So, C. W., Burchell, J., Rahman, K. M., Taylor‑Papadimitriou, J."KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity". International Journal of Oncology 59.5 (2021): 96.
Chicago
Jamshidi, S., Catchpole, S., Chen, J., So, C. W., Burchell, J., Rahman, K. M., Taylor‑Papadimitriou, J."KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity". International Journal of Oncology 59, no. 5 (2021): 96. https://doi.org/10.3892/ijo.2021.5276
Copy and paste a formatted citation
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Spandidos Publications style
Jamshidi S, Catchpole S, Chen J, So CW, Burchell J, Rahman KM and Taylor‑Papadimitriou J: KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity. Int J Oncol 59: 96, 2021.
APA
Jamshidi, S., Catchpole, S., Chen, J., So, C.W., Burchell, J., Rahman, K.M., & Taylor‑Papadimitriou, J. (2021). KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity. International Journal of Oncology, 59, 96. https://doi.org/10.3892/ijo.2021.5276
MLA
Jamshidi, S., Catchpole, S., Chen, J., So, C. W., Burchell, J., Rahman, K. M., Taylor‑Papadimitriou, J."KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity". International Journal of Oncology 59.5 (2021): 96.
Chicago
Jamshidi, S., Catchpole, S., Chen, J., So, C. W., Burchell, J., Rahman, K. M., Taylor‑Papadimitriou, J."KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity". International Journal of Oncology 59, no. 5 (2021): 96. https://doi.org/10.3892/ijo.2021.5276
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