MDMX - A NOVEL P53-BINDING PROTEIN WITH SOME FUNCTIONAL-PROPERTIES OFMDM2

Here we report the isolation of a cDNA encoding a new p53-associating protein. This new protein has been called MDMX on the basis of its str uctural similarity to MDM2, which is especially notable in the p53-bin ding domain. In addition, the putative metal binding domains in the C- terminal part of MDM2 are completely conserved in MDMX. The middle par t of the MDMX and MDM2 proteins shows a low degree of conservation, We can show by co-immunoprecipitation that the MDMX protein interacts sp ecifically with p53 in vivo. This interaction probably occurs with the N-terminal part of p53, because the activity of the transcription act ivation domain of p53 was inhibited by co-transfection of MDMX. Northe rn blotting showed that MDMX, like MDM2, is expressed in all tissues t ested, and that several mRNAs for MDMX can be detected, Interestingly, the level of MDMX mRNA is unchanged after UV irradiation, in contrast to MDM2 transcription. This observation suggests that MDMX may be a d ifferently regulated modifier of p53 activity in comparison with MDM2. Our study indicates that at least one additional member of the MDR;I protein family exists which can modulate p53 function.