| abstract |
The invention relates to assays for identifying modulators of p53Âubiquitination by CUL4 E3 ligase complexes. This assays allows detection of agents and compounds that affect p53 ubiquitination and thus, cell cycle regulation and cell survival in cells. In some assays, an increase in ubiquitination, in comparison to a test sample lacking a test compound, indicates a stimulation of p53 ubiquitination activity, whereas a reduction in p53 ubiquitination indicates an inhibitor of activity. The assays provided may be suited, for example, for high-throughput screening of agents. The invention further relates to methods of modulating p53 activity in a cell, such as a cell of a mammal, by administering agents which decrease expression or activity of a member of a CUL4 E3 ligase complex, or which block the binding of p53 to a CUL4 E3 ligase complex. |