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Lookup NU author(s): Dr John Anderson, Professor Robert Lightowlers, Professor John LunecORCiD
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MDM2 is a pleuripotent 90kDa nucleo-phospho-protein that binds p53 and other proteins contributing to its oncogenic properties. Its structure includes an amino proximal p53 binding site, a central 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 and the previously defined RNA consensus sequence. DNA binding appears selective, MDM2 dependent 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 oligo purine:pyrimidine- rich stretches. Our results suggest that the observed selective 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.
Author(s): Challen C, Anderson JJ, Chranowska-Lightowlers ZMA, Lightowlers RN, Lunec J
Publication type: Article
Publication status: Published
Journal: Nucleic Acids Research - Dual first author paper submitted 19th July 2007
Year: 2007
