Recombinant human MDM2 oncoprotein shows sequence composition selectivity for binding to both RNA and DNA

  • Authors:
    • Christine Challen
    • John J. Anderson
    • Zofia   M.A. Chrzanowska‑Lightowlers
    • Robert N. Lightowlers
    • John Lunec
  • View Affiliations

  • Published online on: November 21, 2011     https://doi.org/10.3892/ijo.2011.1267
  • Pages: 851-859
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Abstract

MDM2 is a 90 kDa nucleo-phosphoprotein that binds p53 and other proteins contributing to its oncogenic properties. Its structure includes an amino proximal p53 binding site, a central acidic domain and a carboxy region which incorporates Zinc and Ring Finger domains suggestive of nucleic acid binding or transcription factor function. It has previously been reported that a bacculovirus expressed MDM2 protein binds RNA in a sequence-specific manner through the Ring Finger domain, however, its ability to bind DNA has yet to be examined. We report here that a bacterially expressed human MDM2 protein binds both DNA as well as the previously defined RNA consensus sequence. DNA binding appears selective and involves the carboxy-terminal domain of the molecule. RNA binding is inhibited by an MDM2 specific antibody, which recognises an epitope within the carboxy region of the protein. Selection cloning and sequence analysis of MDM2 DNA binding sequences, unlike RNA binding sequences, revealed no obvious DNA binding consensus sequence, but preferential binding to oligopurine:pyrimidine-rich stretches. Our results suggest that the observed preferential DNA binding may occur through the Zinc Finger or in a charge-charge interaction through the Ring Finger, thereby implying potentially different mechanisms for DNA and RNA MDM2 binding.

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March 2012
Volume 40 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Challen C, Anderson JJ, Chrzanowska‑Lightowlers ZM, Lightowlers RN and Lunec J: Recombinant human MDM2 oncoprotein shows sequence composition selectivity for binding to both RNA and DNA. Int J Oncol 40: 851-859, 2012
APA
Challen, C., Anderson, J.J., Chrzanowska‑Lightowlers, Z.M., Lightowlers, R.N., & Lunec, J. (2012). Recombinant human MDM2 oncoprotein shows sequence composition selectivity for binding to both RNA and DNA. International Journal of Oncology, 40, 851-859. https://doi.org/10.3892/ijo.2011.1267
MLA
Challen, C., Anderson, J. J., Chrzanowska‑Lightowlers, Z. M., Lightowlers, R. N., Lunec, J."Recombinant human MDM2 oncoprotein shows sequence composition selectivity for binding to both RNA and DNA". International Journal of Oncology 40.3 (2012): 851-859.
Chicago
Challen, C., Anderson, J. J., Chrzanowska‑Lightowlers, Z. M., Lightowlers, R. N., Lunec, J."Recombinant human MDM2 oncoprotein shows sequence composition selectivity for binding to both RNA and DNA". International Journal of Oncology 40, no. 3 (2012): 851-859. https://doi.org/10.3892/ijo.2011.1267