| 摘要 |
Mdm2 binds to p53 in cells in which mdm2 is not overexpressed, i.e. in cells in which mdm2 is expressed at normal or low levels, and this interaction targets p53 for degradation. The present invention exploits this mechanism of p53 degradation to stabilise a substance comprising a mdm2 binding domain linked to a coupling partner in cells in which this mdm2 mediated degradation pathway does not operate efficiently. In contrast, in normal cells expressing functional mdm2, the substance will tend to be unstable as it will be marked for degradation through the interaction of the endogenous mdm2 with the mdm2 binding domain of the substance. Accordingly, the substances can be used to deliver the coupling partner to such cells, e.g. for use in the diagnosis and/or treatment of cancer, viral infections or other conditions associated with non functional p53 or mdm2.
|
